CN1134173A - 间日疟原虫和镰状疟原虫红细胞结合蛋白的结合区 - Google Patents
间日疟原虫和镰状疟原虫红细胞结合蛋白的结合区 Download PDFInfo
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Abstract
本发明提供了在治疗和阻止由镰状疟原虫或间日疟原虫引起的疟疾中有用的分离的多肽。特别是来自EBL家族中的蛋白质的结合区以及镰状疟原虫裂殖子上唾液酸结合蛋白(SABP)的多肽。也可以是来自间日疟原虫裂殖子上Duffy抗原结合蛋白(DABP)的多肽。
Description
发明背景
每年有200-400百万人感染疟疾,引起1-2百万人死亡,因此疟疾是世界上现存的最严重要的感染性疾病之一。在非洲乡村,年龄在一到四岁之间的儿童总死亡数中有大约25%由疟疾引起。由于该疾病作为一种世界研究性健康问题的严重性,人们花费了相当大的努力来鉴定和研究疟疾疫苗。
人类的疟疾由寄生疟原虫属的四个种引起:镰状疟原虫,间日疟原虫,P.knowlesi和三日疟原虫。人类疟疾的主要起因是镰状疟原虫,它每年感染200百万到400百万人,导致1到4百万人死亡。
间日疟原虫(人类的四种感染性疟原虫之一)不能在体外培养,而P.knowlesi(在东半球猴中发现的疟疾品种,也侵入人红细胞)和镰状疟原虫能。尽管间日疟原虫与P.knowle-si在系统发育上基本相似,但两个品种在许多重要方面不同。例如:间日疟原虫对许多猿猴种类不感染且在其它种类中不易形成感染,而P.knowlesi不易感染人类但容易感染许多猿猴种类。
抗疟疾的各种有效疫苗的基础鉴别是通过了解该寄生虫的生存周期来实现的。当幼龄疟疾寄生虫或“子孢子”被蚊注射进人的血液中时感染人类。注射后,寄生虫定位于肝细胞。大约一周后,寄生虫或“裂殖子”释放进血液中。寄生虫进入血液后开始“红细胞”期。每个寄生虫进入红血细胞以便生长和发育。当裂殖子在红血细胞中成熟时,将它称为滋养体,滋养体进行几轮核分裂(裂殖生殖)直到使红细胞破裂,释放6到24个裂殖子。经过几个无性裂殖生殖循环后,有些寄生虫发育成称为“配子母细胞”的形态学上明显不同的形式,其寿命长且进行有性发育以代替通过有性繁殖产生的裂殖体。
疟原虫的有性发育涉及雌性或“大配子母细胞”和雄性疟原虫或“小配子母细胞”。这些配子母细胞在人体内不进行进一步的发育。当配子母细胞摄入到蚊体内后,在蚊中肠开始复杂的有性循环。10到20分钟后红血细胞在纹中肠分裂。小配子母细胞通过小配子形成继续发育并释放8个鞭毛丰富的小配子母细胞。受精通过大配子母细胞和小配子母细胞的融合实现。受精的疟原虫称为受精卵,由它发育成“动合子”。动合子包埋于蚊中肠,在那里转化成卵母细胞,形成许多小孢子。在包埋于中肠之前,动合子必须首先穿透围食膜,围食膜明显充当摄入的疟原虫入侵的屏障。卵母细胞破裂成小孢子,经血淋巴迁移到蚊唾液腺。一旦进入蚊唾液,疟原虫可被注射进宿主体内。
疟原虫属生活史的红细胞期与疫苗发展特别相关,因为宿主疟疾的临床和病理特征归因于这一阶段。在间日疟原虫和P.knowlesi中,存在于Duffy阳性红细胞上的Duffy血型决定簇是侵入人红细胞所必需的(Miller et al.,Science 189:561-563,(1975);Miller et al.,N.Engl.J.Med.295:302-304,(1976))。在镰状疟原虫中,裂殖子侵入红细胞似乎取决红细胞上血型糖蛋白唾液酸的结合(Miller,et al.,J.Exp.Med.146:277-281,(1971);Pasvol,et al.,Lancet.,ii:947-950(1982);Pasvol,et al.,Nature,279:64-66(1982);Perkins,J.Exp.Med.160:788-798(1984))。以猴疟原虫P.knowlesi进行的研究使人们能更清楚地了解侵入过程中发生的多个事件。很可能尽管间日疟原虫和镰状疟原虫分别与Duffy抗原和唾液酸结合,但它们互相间及与P.knowlesi以相同的方式进行侵入。
对于P.knowlesi在侵入过程中,裂殖子首先以裂殖子的任一表面附着于红细胞上,然后重新调整方向以便其顶端与红细胞接触(Dvorak et al.,Science 187:748-750(1975)。裂殖子的附着和重新取向在Duffy阳性和Duffy阴性细胞上能同等顺利地进行。然后在裂殖子顶端和Duffy阳性红细胞间形成连接,随后形成液泡,裂殖子进入液泡(Aikawa etal.,J.Cell Biol.77:72-82(1978))。在Duffy阴性细胞上不发生连接形成和裂殖子进入红细胞(Miller et al.,J.Exp.Med.149:172-184(1979),认为Duffy决定簇特异性受体与顶端连接形成而不是起始附着有关。
以3种细胞器的存在定义裂殖子的顶端:rhopteries,密集颗粒和微丝体。在液泡形成时rhopteries和密集颗粒释放其内含物(Ladda et al.,1969;Aikawa et al.,J.Cell Biol.,77:72-82(1978);Torn et al.,Infection and Immunity 57:3230-3233(1989);Bannister and Dluzewski,Blood Cell 16:257-292(1990)。到目前为止微丝体的功能尚不清楚。然而,微丝体的位置表明它们与侵入过程有关。Duffy抗原结合蛋白(DABP)和唾液酸结合蛋白(SABP)已分别定位于P.knowlesi和镰状疟原虫的微丝体上(Adams et al.,cell 63:141-153(1990);sim et al.,Mol.Biochem.Parasitol.51:157-160(1992))。
DABP和SABP是可溶蛋白质,在感染的红细胞释放裂殖子后它们出现在培养物上清液中。免疫化学资料表明DABP和SABP分别是间日疟原虫和镰状疟原虫在红细胞上Duffy和唾液酸受体的配体,在可溶或膜结合形式下具有同样的结合特异性。
DABP是135KDa的蛋白质,它与Duffy血型决定簇特异性地结合(Wertheimer et al.,Exp.Parasitol.69:340-350(1989);Barnwell,et al.,J.Exp.Med.169:1795-1805(1989))。因此,DABP与人Duffy阳性红细胞的结合是具有特异性的。人红细胞有4种主要Duffy表型:Fy(a),Fy(b),Fy(ab)和Fy(阴性),以抗Fya和抗-Fyb血清来定义(Hadley et al.,In Red Cell A ntigens and Antibodies.G.Garrat-ty,ed.(Arlingten,Va:American Association of Blood Banks)PP.17-33(1986)。DABP同等地与Fy(a)和Fy(b)红细胞结合(两类红细胞对间日疟原虫的感染同样敏感)而不与Fy(阴性)红细胞结合。
至于SABP,它是175KDa的蛋白质,与红细胞上血型糖蛋白的唾液酸残基特异性地结合(Camus and Hadley,Science230:553-556(1985);Orlandi,et al.,J.Cell Biol.116:901-909(1992))。因此,神经氨酸苷酶处理(裂解唾液酸残基)使红细胞对镰状疟原虫的侵入具有免疫力。
结合的特异性和与疟原虫感染的相关性表明DABP和SABP是间日疟原虫和镰状疟原虫的与唾液酸和红细胞上的Duffy抗原相互作用的蛋白质。编码两种蛋白质的基因已被克隆、已测定了该DNA和预期的蛋白质序列(B.Kim Leesim,et al.,J.Cell Biol.111:1877-1884(1990);Fang.X.,et al.,Mol.Biochem Parasitol,44:125-132(1992))。
尽管全世界做出了相当大的研究努力,但由于疟原虫的复杂性和其与宿主的相互作用,还不可能发现用于阻止或抵抗疟疾血液阶段的令人满意的溶液。由于疟疾是一个巨大的世界性健康问题,因此需要抵抗该疾病影响的方法。本发明提供了抗疟原虫属感染的有效的防止和治疗措施。
本发明概述
本发明提供了包含分离的DABP结合区多肽和/或分离的SABP结合区多肽的组合物。DABP结合区多肽优选包含在大约200到大约300之间的氨基酸残基,而SABP结合区多肽优选包含在大约200到大约600之间的氨基酸残基。优选的DABP结合区多肽具有SEQ ID NO.2中所示的残基1到大约325的氨基酸序列。优选的SABP结合区多肽具有SEQ ID NO.4的残基1到大约61 6的氨基酸序列。
本发明还包括包含药用学上可接受的载体和以在生物体内足以诱导抗间日疟原虫裂殖子的保护性免疫反应的量的分离的DABP结合区多肽之药用组合物。而且以足以诱导抗镰状疟原虫保护性免疫反应的量的分离的SABP结合区多肽可加入药用组合物中。
还提供了包含药学上可接受的载体和分离的SABP结合区多肽的药用组合物,其中多肽的量是以在生物体内诱导抗镰状疟原虫的保护性免疫反应。另外,分离的DABP结合区多肽能以足以诱导抗间日疟原虫的保护性免疫反应的量加入药用组合物中。
还公开了编码DABP结合区多肽或SABP结合区多肽的分离的多聚核苷酸。另外,本发明包括含有编码DABP结合区多肽的多聚核苷酸的重组细胞。
本发明进一步包括在病人体内诱导抗疟原虫属裂殖子的保护性免疫反应的方法。该方法包括给病人施用免疫上有效量的药用组合物,该组合物包含药学上可接受的载体和分离的DABP结合区多肽,SABP结合区多肽或其组合。
本说明书还提供来自红细胞结合配体(EBL)家族其它镰状疟原虫基因的DNA序列。该家族具有与镰状原虫175KD和间日疟原虫135KD结合蛋白保守的区域。
定义
本文所用的“DABP结合区多肽”或“SABP结合区多肽”是分别与来自Duffy抗原结合蛋白(DABP)富含半胱氨酸的氨基末端区域或唾液酸结合蛋白(SABP)的序列基本相同(定义如下)的多肽。该多肽能结合Duffy抗原或血型糖蛋白上的唾液酸残基。特别是DABP结合区多肽由与SABP结合区内从N端氨基酸(残基1)到大约残基325的序列基本相似的氨基酸残基组成。SABP结合区多肽由与DABP结合区内从N端氨基酸(残基1)到大约残基616的序列基本相似的残基组成。
由EBL家族基因编码的结合区多肽由与上面定义的DABP和SABP结合区的序列基本相同的那些残基组成。EBL家族包含与DABP和SABP保守区基本相似的序列。它们包括本文以EBL-e1(SEQ ID Nos 5和6),E31a(SEQ IDNos 7和8),EBL-e2(SEQ ID Nos 9和10)和Proj3(SEQ IDNos 11和12)报道的那些序列。
本发明的多肽可由结合区的全长或其片段组成。典型的DABP结合区多肽由以大约50到大约325的残基组成,优选在大约75和300之间,更优选的是在大约100到大约250之间的残基。SABP结合区多肽由从大约50到大约616的残基组成,优选大约75到300之间,更优选的是大约100到大约250之间的残基。
本发明特别优选的多肽是那些位于结合区内的多肽,该结合区在SABP和EBL家族之间保守。这些保守的区域内的残基如下面图1所示。
当进行最大相关性序列对比时,如果两个序列中的核苷酸或氨基酸残基序列相同时两个多聚核苷酸或多肽说成是“相同的”。可用局部同源性公式(Smith and Waterman,Adv.Appl.Math.2:487(1981),同源性排列公式(Needleman andWunsch,J.Mol.Biol.48:443(1970))相似性寻找方法(Pearson and Lipman,Proc Natl Acad.Sci(U.S.A)85:2444(1988),这些公式计算机化的程序(GAP,BESTFIT,FASTA,and TFASTA in the Wisconsin Genetics Software Packag,Genet-ics Computer Group,575 Science Dr.,Madison,WI)或经检查来进行序列比较的最佳排列。本文引用这些文献以供参考。
术语“基本上相同”指多肽包含的序列与对照序列相比(通过比较大约20个残基至大约600个残基,典型的是大约50到大约500个残基,通常是大约250到300个残基)具有至少80%的序列相同性,优选90%,更优选的是95%或更多。使用上面程序测定相同百分数的值。本发明特别优选的多肽包含的序列中至少存在在DABP和SABP中保守的半脱氨酸残基的70%。另外,该多肽包含的序列至少有在DABP和SABP保守的色氨酸残基的50%存在。考虑到在DABP,SABP和EBL家族的序列之间发现的那些保守的氨基酸残基,本文还具体定义了术语基本相似。这些保守的氨基酸主要由在本文报道的所有序列中保守的色氨酸和半脱氨酸残基组成。其它保守的氨基酸残基包括苯丙氨酸残基,它可用酪氨酸取代。本领域的技术人员使用上面所列方法进行序列对比后可测定这些氨基酸残基是保守的。
多肽序列基本相同的另一解释是一种蛋白质是否与产生的抗其它蛋白质的抗体发生免疫反应。因此,本发明的多肽包括与产生的抗SABP结合区,DABP结合区或产生的抗EBL家族保守区的抗体发生免疫反应的多肽。
核苷酸序列基本相同的另一解释是2种分子是否在严格条件下互相杂交。严格条件具有序列依赖性并在不同的环境下会有差别。一般来说,严格条件的选择是在限定离子强度和ph下列入下比特定序列的热熔点(Tn)大约约5℃。Tm是50%的靶序完全匹配的探针杂交的温度(在限定的离子强度和ph下)。典型的严格条件是在pH7下盐浓度至少为大约0.02摩尔,温度至少为大约60℃。
短语“分离的”或“生物学纯的”指物质基本上或必须没有在基天然状态下通常与其共存的成份。因此,本发明的结合区多肽不含正常情况下与其原位环境相联的物质,例如,裂殖子膜的其它蛋白质。然而,即使蛋白质经PAGE分离成均质或占优势的带,可能仍有5-10%范围的与所需蛋白质共同纯化的天然蛋白质的微量污染。本发明分离的多肽不含这类内源性共同纯化的蛋白质。
蛋白质的纯度或匀质性可用许多本领域公知的方法来表示,如蛋白质样品的聚丙烯酰胺凝胶电泳,接着经染色进行肉眼观察。对于某些用途需要高分辩率,可使用HPLC或相似的纯化方法。
术语“残基”指以酰胺键或酰胺键类似物掺入寡肽的氨基酸(D或L)或氨基酸类似物。本发明的酰胱键类似物包括本领域的技术人员公知的肽骨架修饰。
附图的简要描述
图1显示了DABP结合区(间日疟原虫),2个同源SABP区(SABP F1和SABP F2)和EBL基因家族测序的成员(ebl-e1,E31a,EBL-e2和三个同源Proj3区)预期氨基酸序列的序列对比。
图2显示PRE4克隆载体的图示。
图3显示了在分离编码本发明保守区的序列中有用的引物。
优选实施例方案的描述
裂殖子和裂殖体红细胞的结合是由裂殖子或裂殖体表面的特异性结合蛋白介导的,它对红细胞的感染是必需的。对于镰状疟原虫,这种结合涉及红细胞上唾液酸血型糖蛋白残基与裂殖子或裂殖体表面的唾液酸结合蛋白(SABP)之间特异性的相互作用。纯化的SABP结合具有化学或酶修饰的唾液酸残基的红细胞的能力与镰状疟原虫感染这些红细胞的能力相平行。而且,唾液酸缺陷型红细胞既不结合SABP,也不能被镰状疟原虫感染。还克隆和侧序了编码镰状疟原虫SABP的DNA。
在间日疟原虫中,与红细胞的特异性结合涉及红细胞上Duffy血型抗原与裂殖子上Duffy抗原结合蛋白(DABP)之间的相互作用。Duffy结合蛋白在生物学上定义为感染的红细胞释放裂殖子后在培养物上清液中出现的那些可溶性蛋白质,它与人Duffy阳性红细胞结合,而不与人Duffy阴性红细胞结合。显示了间日疟原虫DABP蛋白质与Duffy阴性红细胞的结合被抗Duffy血型决定簇的抗血清抑制。纯化的Duffy血型抗原也抑制与红细胞的结合。Western印迹也显示DABP与Duffy血型决定簇结合。
人红细胞上的Duffy阳性血型决空簇对间日疟原虫引起的人红细胞的感染是必需的。间日疟原虫裂殖子的附着和重新取向在Duffy阳性和阴性红细胞上同等顺利地发生。然后在裂殖子顶端和Duffy阳性红细胞之间形成联接,接着形成液泡且裂殖子进入液泡。在Duffy阴性细胞上不发生连接的形成和裂殖子进入红细胞,这表明Duffy决定簇特异性的受体与顶端连接的形成而不是与起始附着有关。克隆和侧序了编码间日疟原虫和P.knonlesi DABP的DNA序列。
间日疟原虫的红细胞感染绝对需要Duffy血型抗原。然而,镰状疟原虫分离物的感染对唾液酸的依赖性不同。建立了一些以正常频率感染唾液酸缺陷型红细胞的镰状疟原虫克隆。这表明镰状疟原虫的一些菌株能与红细胞上的其它配体相互作用,因此可能有多种具有不同特异性的红细胞结合蛋白。
本发明的基础是在DABP和SABP上发现了结合区。DABP和SABP预期的蛋白质序列比较揭示了在两种蛋白质之间具有高度相似性,在两种蛋白质中有一个氨基末端富含半胱氨酸的区域。DABP氨基末端的富含半胱氨酸的区域含大约325个氨基酸,而SABP氨基末端的富含半胱氨酸的区域含大约616个氨基酸。这是由于在SABP蛋白质的氨基末端半胱氨酸富集区有明显的重复。在SABP和DABP的2个区域之间半胱氨酸残基周围的氨基酸和许多芳香族氨基酸残基也一样。氨基末端的半胱氨酸富集区和靠近羧基末端的另一半胱氨酸富集区表明在DABP和SABP蛋白质之间最相似。这2个半胱氨酸富集区之间的氨基酸序列区域表明在DABP和SABP之间仅有有限的相似性。
鉴定了其它具有与SABP和DABP结合区基本相同的区域的镰状疟原虫开架阅读框和基因。这些序列在疟原虫基因组中存在多个拷贝表明它们在宿主-疟原虫的相互作用中具有重要活性。从染色体7的亚片段文库中克隆了这些序列的一个家族(EBL家族),该文库在氯奎抗性基因座的遗传研究中构建(Wellems et.al.,PNAS 88:3382-3386(1991))。EBL序列的对比鉴定了镰状疟原虫175KD蛋白质中高度保守的区域;这些保守区接着用于鉴定其中之一(ebl-e1)位于染色体13的基因(ebl-e1,ebl-e2)。连锁遗传研究将该基因定位在染色体13影响疟原虫感染人红血细胞的区域上(Wellems et al.,Cell 49:633-642(1987))。
使用来自这些开架阅读框的探针进行的Southern杂交实验表明这些保守序列有额外的拷贝位于基因组的其它位置。染色体7上最大的开架阅读框是8千碱基,含4个与SABP和DABP N端半胱氨酸富集单位同源的串联重复。
图1代表EBL家族与DABP结合区和2个SABP同源在(F1和F2)的序列比较。将EBL家族分成2个亚家族以获得最佳序列比较。保守的半胱氨酸残基以黑体字显示,保守的芳香族残基下面划线。
本发明的多肽可用于产生SABP,DABP结合区域EBL基因家族保守区特异性的单克隆抗体。该抗体可用于疟疾感染的诊断或作为治疗试剂抑制裂殖子与红细胞的结合。抗所需抗原的单克隆抗体的生产对本领域的技术人员而言是公知的,在本文不再详细描述。
本领域的技术人员,可得到的用于生产和控制各种免疫球蛋白”和“抗体”,指由一种或多种基本上由免疫球蛋白分子的许多技术可轻易地用来控制结合。本文所用的术语“免疫球蛋白基因编码的多肽组成的蛋白质。除抗体外,免疫球蛋白能以各种形式存在,例如包括Fv,Fab,和F(ab)2以及以单链的形式存在。免疫球蛋白结构和功能的一般知识见基础免疫学(第二版,W.E.Paul编辑,Ravens出版,纽约(1989))。
与本发明的多肽结合的抗体可用各种方法来生产。非人类单克隆抗体(例如鼠、兔形目、马等)的生产是公知的并且可用(例如)以含该多肽的制品免疫动物来完成。使从免疫的动物获得的抗体生产细胞成为永生细胞并进行筛选,或者先筛选以生产控制裂殖子和红细胞结合的抗体,然后使成的永生细胞。单克隆抗体生产一般方法的讨论见Harlow和Lane的《抗体,实验室手册》Cold Spring Harbor出版,纽约(1988)。
因此,本发明能达到保护性免疫反应的目的或得到单克隆抗体以侧序在SABP、DABP和EBL基因家族编码区之间保守的结合区。这些蛋白质结合区的鉴定有助于形成疫苗,因为它使人们得以将精力集中在大分子的功能单元上。从结合区内特定序列优选出在进化中保守的关键区域的目标,于是优选用作抗疟原虫的疫苗。
EBL家族的基因(以前尚来侧序)可用作标记来检测病人中镰状疟原虫的存在。使用症状性病人的组织或血液与EBL家族基因片段互补的寡核酸进行PCR反应,以本领域的实践者熟知的方法可完成这种检测。而且,测序的EBL家族为熟练的实践者提供了生产在各种运用中用作遗传标记的限定的探针的一种方法。
另外,本发明定义了一个存在于(但不限于)参与宿主寄生作用的Apicomplexa亚门其它成员中的保守区。可使用图3所示的合成寡聚核苷酸引物以聚合酶链式反应在疟原虫种类和其它寄生的原生动物中鉴定该区域。PCR方法在下文中详细描述。从DABP,SABP和EBL家族中显示出最高保守程序的保守部位的区域设计这些引物。图3显示了这些区域和来自它们的相一致的氨基酸序列。
A.一般方法
本申请中所需的许多命名法和一般实验程序可参见Sambrook等的《分子克隆实验手册》(第2版)(Vo.l1-3)纽约、冷泉港,冷泉港实验室,1989),该手册下文称为“Sam-brook等”。
B.分离编码SABP、DABP和EBL结合区的方法
本发明的核酸组合物,不论是RNA,cDAN,基因组DNA,还是各种组合的杂种,可从天然来源分离或在体外合成。要求保护的核酸可存在于转化的或转染的完整细胞中,在转化的或转染的细胞的溶胞产物中或以部分纯化或基本上纯的形式存在。
编码本发明结合区的基因的核酸操作技术,如将编码多肽的核酸序列亚克隆到表达载体上,标记探针,DNA杂交和类似操作一般在Sambrook等中已有描述,本文引用以供参考。
可使用重组DNA技术生产结合区多肽。一般来说,首先克隆编码SABP和DABP结合区的DNA或以适合物连热闹到表达载体上的形式分离。连接后,含DNA片段或插入物的载体导入合适的宿主细胞以表达重组结合区。然后从宿主细胞中分离多肽。
有许多方法分离编码SABP,DABP和EBL结合区的DNA序列。典型,使用DNA中序列特异性的标记的寡核苷酸探针从基因组或cDNA文库中分离DNA。限制性核酸内切酶消化含合适基因的基因组DNA或cDNA可用来分离编码这些蛋白质结合区的DNA。由于已知SABP和DABP基因的DNA序列,可设计一组限制性核酸内切酶在所需区域裂解该DNA。限制性核酸内切酶消化后,经过其与核酸探针杂交的能力(例如在Soutern印迹上)来鉴定编码SABP结合区域DABP结合区的DNA,使用本领域的技术人员熟悉的标准方法(见Sambrook,et al)分离这些DNA区域。
也可用聚合酶链式反应制备DABP,SABP EBL结合区DNA。聚合酶链式反应技术(PCR)用于直接从mRNA,cDNA基因组文库或cDNA文库中扩增DABP和SABP结合区的核酸序列。对这一方法而言,图3所示的引物是特别优选的。
用于扩增SABP和DABP结合区DNA的合适引物和探针从DNA序列分析中产生。简单地说,合成与所要扩增的DNA区域2个3′端互补的寡核苷酸引物。然后使用这2个引物进行聚合酶链式反应。见PCR Proto cols:A Guide toMethods and Appeicarions Innis,M.Gelfand.D.,Sninsky,J.and White.T.,eds.,Academic Press,San Diego(1990)。根据需要,可选择引物来扩增全部DABP区域或扩增DABP和SABP结合区的小片段。
根据Beaucage,S.L和Caruthers.M.H.首先描述的固相phosphoramidite三酯方法(Tetrahedron Letts.,22(20):1859-1862,1981),使用自动合成仪化学合成用作探针的寡核苷酸,如Needham-VanDevanter,D.R.,et al.1984,NucleicAcids Res.,12:6159-6168中所述。寡核苷酸的纯化经过天然丙烯酰胺凝胶电泳或经过阴离子交换HPLC完成,如Pearson.J.D.and Regnier.F.E.,1983.J.Chrom.,255:137-149中所述。
使用Maxam.A.M和Gilbert的化学降解方法(见W.,Grossman.L.and Moldave,D.,eds.Academic Press,NewYork,Methods in Enzymology,65:499-560)可证实合成的寡核苷酸序列。
本领域的技术人员已知的其它方法也可用于分离编码SABP或DABP结合区的全部或部分的DNA。见Sambrook等。
C.DABP.SABP和EBL结合区多肽的表达
一旦分离和克隆出结合区DNA,可在重组构建的细胞如细菌、酵母,昆虫(特别是使用杆状病毒载体)和哺乳动物细胞中表达所需的多肽。按期望本领域的技术人员知道许多可用于表达编码DABP和SABP结合区的DNA的表达系统。因此不再详细描述已知的在原核或真核细胞中用于表达蛋白质的各种方法。
作为简要的概述,编码结合区的天然或合成的核酸的表达典型地可经过将DNA或cDNA有效连接到启动子上(启动子可以是结构性的或是诱导性的),接着掺入表达载体中来实现。载体可适合于在原核生物或真核生物中复制和整合。典型的表达载体含有对调节编码结合区的DNA的表达有用的转录和翻译终止子,起始序列和启动子。为了获得克隆基因的高水平表达,所需构建的表达质粒最少含有一个指导转录的强启动子,一个用于翻译起始的核糖体结合位点和一个转录/翻译终止子。
1.在原核生物中的表达
在E.coli中适于该目的的调节区例子是Yanofsky,C.,1984,J.Bacteriol.,158:1018-1024中所述的E.coli色氨酸生物合成途径的启动子和操纵子区域和Herskowintz,I.and Hagen,D.,1980,Ann,Rev Genet.,14:399-445所述的N噬菌体(PL)的左向启动子。转化进E.coli中的DNA载体包含有选择标记也是有用的。这类标记的例子包括编码氨苄青霉素,四环素或氯霉素抗性的基因。见Sambrook等关于在E.coli中使用的选择标记的详细描述。
载体的选择应使之能导入合适的宿主细胞。细菌载体是典型的质粒或噬菌体来源。用噬菌体载体颗粒感染或用裸露的噬菌体载体DNA转染合适的细菌细胞。如果使用质粒载体,用质粒载体DNA转染细菌细胞。
可使用E.coli.Bacillus sp.(Palva,I et al.,1983,Gene22:229-235;Mosbach,K.et al.Nature,302:543-545)和沙门氏菌优选E.coli系统。
原核细胞产生的结合区多肽可能不会正确地折叠。在从E.coli中纯化的过程中,表达的多肽可能光变性,然后再复性。这可经过将细菌产生的蛋白质溶于离液剂如盐酸胍中并用还原剂如β-巯基乙醇还原全部半胱氨酸残基来实现。然后经缓慢透折或凝胶过滤使多肽复性。见美国专利号4511503。
表达抗原的检测经过本领域已知的方法如放射免疫试验,Western印迹技术或免疫沉淀法来实现。从E.coli中的纯化可按美国专利号4511503所述的程序进行。
2.SABP,DABP和EBL结合区在真核生物中的合成
本领域的技术人员已知各种真核表达系统,如酵母、昆虫细胞和哺乳动物细胞。正如下面所作的简要描述,DABP和SABP结合区也可在这些真核系统中表达。
a.在酵母中的表达
异源蛋白质在酵母中的合成是人们所熟知的且有较好的描述。Methods in Yeast Genetics,Sherman,F.,et al.,Coldspring Harbor Laboratory,(1982)是一部较好的论著,描述了在酵母中生产结合区可用的各种方法。
用于酵母的启动子例子包括GAL.,10(Johnson,M.,and Davies,R.W.,1984,Mol.and Cell,Biol.,4:1440-1448)ADH2(Russell,D.,et al.1983,J.Biol,Chem.,258:2674-2682).PHO5(EMBO J.6:675-680,1982)和MFa1(Herskowitz,Iand Oshima,Y.,1982 in The Molecular Bi-ology of the Yeast Saccharomyces,(eds,Strathern,J.N.Jones,E.W.,and Broach,J.R.,Cold Spring Harbor Lab.,Cotd Sp[ring Harbor.N.Y.,PP 181-209).也可使用具有选择性标记的多拷贝质粒,如Leu-2,URA-3,Trp-1,和His-3。
许多酵母表达质粒(如YEp6,YEpb,YEp)可用作载体。可将目的基因与各种酵母载体中的任一启动子融合。上述质粒在文献中已做了充分描述(Botstein,et al.,1979,Gene,8:17-24;Broach,et al.,1979,Gene,8:121-133)。
在转化酵母细胞中使用2种方法。在一种情况下,首先使用Zymolyase,溶细胞酶或glusulase将酵母细胞转化为原生质体,接着加入DNA和聚乙二醇(PEG)。然后在选择性条件下在3%的琼脂培养基中再生PEG处理的原生质体。在文章(J.D.Beggs,1978,Nature(London).275:104-109;和Hinnen,A.,et al.,1978,Proc.Natl.Acad.Sci.USA,75:1929-1933)中给出了该方法的细节。第二种方法不涉及去掉细胞壁。而是将细胞用氯化锂或乙酸及PEG处理并涂布在选择性培养板上(Ito,H.,et al.,1983.J.Bact.,153:163-168)。
经过溶融细胞并对溶胞产物运用标准蛋白质分离技术可以酵母中分离结合区。经过使用Western印迹技术或其它标准免疫测定技术的放免试验可实现对纯化过程的监测。
b.在哺乳动物和昆虫细胞培养物中的表达
对生产结合区有用的细胞培养物的例子有昆虫或哺乳动物起源的细胞。哺乳动物细胞系统常以细胞单层的形式使用,尽管也可使用哺乳动物细胞悬液。哺乳动物细胞系的例子包括VERO和Hela细胞,中国仓鼠卵巢(CHO)细胞系,W138,BHK.Cos-7或MDCK细胞系。
如上面所述,用于转化宿主细胞的载体(例如质粒)优选含起动转录的DNA序列和控制抗原基因序列翻译的序列。这些序列称为表达控制序列。当宿主细胞是昆虫或哺乳动物起源的细胞时,表达控制序列的例子是得自SV-40启动子(Science,222:524-527,1983),CMV I.E.启动子(Proc.Natl.Acad.Sci.81:659-663,1984)或金属硫蛋白启动子(Nature 296:39-42,1982)的序列。使用限制性酶裂解含表达控制序列的克隆载体,如果必要或需要的话调节其大小并以本领域熟知的方法与编码SABP或DABP多肽的DNA连接。
与酵母一样,当使用更高等动物的宿主细胞时,需要将已知哺乳动物基因的多聚腺苷化或转录终止子序列掺入载体中。终止子序列的例子是牛生长激素基因的多聚腺苷酸化序列。还应包括对转录子进行精确剪接的序列。剪接序列的例子是SV40的VP1内含子(sprague J.et al.,1983,J.Virol.45:773-781)。
另外,可向载体中掺入在宿主细胞中控制复制的基因序列,例如在牛乳头状瘤病毒类型载体中发现的序列(Saveria-Campo.M.,1985,“Bovine Papilloma viras DNA a EudargoticCloning Veitor”in DNA Cloniry Vol.II a praitical Approach Ed.D.M.Glover.IRL Press.Arlington.Virginia pp.213-238)。
为了进行转化,宿主细胞应是感受态或经过各种方法使其成为感受态。有一些熟知的方法诱导DNA进入动物细胞。这些:磷酸钙沉淀法,将受体细胞含DNA的细菌原生质体融合,用含DAN的脂质体处理受体细胞,DEAE葡聚糖,电穿孔和将DNA直接显微注射进细胞。
以本领域,已知的方法培养转化的细胞(BiochenicalMethods in Cell Culture and Virologg,Kuchler,R.J.Dowden,Hutchinson and Ross.Inc.(1977)。从以悬液或单层生长的细胞中分离表达的DABP和SABP结合区多肽。对于单层的回收使用熟知的机械,化学或酶方法。
c.在重组牛痘病毒或腺病毒感染的细胞中表达
除了在重组表达系统中使用外,分离的结合区DNA序列也可用于转化在病人中的转染宿主细胞的病毒。活的减毒病毒(如牛痘或腺病毒)是疫苗的常规选择,因为它们生产成本低且易于运输和施用。在免疫方法中有用的牛痘载体和方法已有描述,例如美国专利号422848,本文引用以供参考。
用于本发明的合适的病毒包括(但不限于)痘病毒(如金丝雀痘和牛痘病毒),牛痘病毒,α病毒,腺病毒和其它动物病毒。可使用本领域熟知的方法生产重组病毒,例如使用同源重组或连接工种质粒的方法。例如,重组金丝雀痘或奶牛痘病毒的制备可经过将编码DABP和SABP结合区多肽的DNA插入质粒,使其两端以病毒序列为侧翼。然后通过同源重组将编码结合区的DNA插入病基因组中。
例如,重组腺病毒的生产可经过将各含大约50%病毒序列的2种质粒与编码红细胞结合区多肽的DNA序列连接起来。重组RNA病毒(如α病毒)的制备可使用本领域已知的方法经CDNA介导制备。
到于牛痘病毒(例如WR株),经过包括同源重组的许多方法,使用转移载体pTKgpt-OFIS可将编码结合区的DNA序列插入基因组中,如Kaslow.et al.,Science 252:1310-1313(1991)中所述,本文引用以供参考。
作为选择,编码SABPS和DABP结合区的DNA可插入另一设计的质粒(例如PGS62)中以生产重组中痘(Langford,C.L.,et al.,1980,Mol.Cell.Biol.6:3191-3199)。这种质粒由用于插入外源基因的克隆位点,指导插入基因合成的痘P7.5启动子和在外源基因两端侧翼的牛痘TK基因组成。
可使用编码DABP和SABP结合区多肽的cDNA经DNA杂交和使用表达结合区多肽特异性的抗体经免疫检测技术来进行重组病毒生产的证实。病毒种子的制备可经过感染细胞(例如HELA S3旋转细胞)并收获病毒子代实现。
本发明的重组病毒可用于哺乳动物(如小鼠或人类)中诱导抗—SABP和抗—DABP结合区抗体。另外,可经过体外感染宿主细胞,该宿主细胞随后表达多肽来将重组病毒用于生产SABP和DABP结合区(见上面SABP和DABP结合区在真核细胞中的表达部分)。
本发明还涉及用重组病毒感染的宿主细胞。本发明的宿主细胞优选哺乳动物,如BSC-1细胞。以重组病毒感染的宿主细胞在其细胞表面表达DABP和SABP结合区。另外,当用于接种或加强预先接种的哺乳动物时,感染细胞的膜提取物诱导保护性抗体。
D.SABP,DABP和EBL结合区多肽的纯化
重组DNA技术产生的结合区多肽可使用本领域的技术人员熟知的标准技术来纯化。重组产生的结合区多肽可直接表达或以融合蛋白质的形式表达。然后将细胞溶合(例如声处理)和亲合色谱结合使用来纯化蛋白质。对于融全产物,随后用合适的蛋白裂解酶消化融合蛋白以释放所需的SABP和DABP结合区。
本发明的多肽可用本领域熟知的标准技术纯化成基本纯的产品,这些技术包括用诸如硫酸铵的物质进行选择性沉淀,柱色谱免疫纯化方法和其它方法。例如,见R.Scopes.Pro-tein Purifieation:Principles and Practice,Springer-Velag:NewYork(1982),本文引用以供参考。
E.以蛋白质化学技术生产结合区
可用大量各种各样的方法结合成制备本发明的多肽。例如:大小相当短的多肽可按常规技术在溶液中或在固体支持物上合成。各种自动合成仪可以商品的形式买到并根据已知的方法使用,例如见Stewart and Young,Solid Pharse PeptideSynthesis,2d.ed.,Pierce Chemical Co.(1984)。
作为选择,可蛋白裂解酶处理纯化的和分离的SABP,DABP或EBL家族蛋白质以生产结合区多肽。例如,重组DABP和SABP蛋白质可用于该目的。然后可分析DABP和SABP蛋白质的序列以选择蛋白裂解酶,用于生产含DABP和SABP结合区的所需区域的多肽。然后经过使用蛋白质和肽纯化的标准技术纯化所需多肽。至于标准技术,可见Meth-ods in Enzymology,“Guide to Protein Purification”M.Deutscher,ed.Vol.182(1990),Page 619-626,本文引用以供参考。
F.核酸和多肽序列的修饰
用于转染宿主细胞以生产重组结合区多肽的核苷酸序列可标准技术进行修饰以产生是有各种所需特征的结合区多肽。本发明的结合区多肽经使用本领域的技术人员熟知的各种重组DNA技术可较容易的设计和生产。例如可以氨基酸插入,取代,缺失和类似技术从天然存在的序列在一级结构水平上改变结合区多肽。可使用这些修饰的许多组合以生产最终的修饰的蛋白质链。
可据各种主观目的制备氨基酸序列的变异体,包括利于纯化和制备的重组多肽。修饰的多肽对于改变血桨半衰期,提高治疗效力和降低治疗使用中副作用的严重性或发生率也是有用的。氨基酸序列变异体通常是预先确定的变异体,它在自然是中不存在但与天然存在的多肽表现出相同的免疫活性。例如,可生产仅包含一级结构一部分(通常是至少大约60-80%,典型的是90-95%)的多肽片段。为用作疫苗,典型的多肽片段的长度应优选至少保留一个能诱导封闭抗体生产的抗原决定基。
一般来说编码结合区多肽序列的修饰应以各种熟知的技术易于完成,如用定点突变技术(见.Giliman and Smith,Gene 8:81-97(1979)and Roberts.S.et al.,Nature 328;731-734(1987))。一个普通技术人员将感到许多突变的效果难以预料。因此大多数修饰在争对所需特征的合适试验中经常规筛选来评价。例如,多肽免疫特征的改变可用合适的竞争性结合试验来检测。其它特征的修饰,如氧化还原或热稳定性,疏水性,对蛋白裂解的敏感性或凝集倾向性都可根据标准技术来测定。
G.诊断和筛选试验
本发明的多肽可用于在生物样品中裂殖子检测的诊断学应用。使用一些较好识别的以免疫结果为基础的特异性结合试验可检测寄生物的存在(见美国专利4366241;4376110;4517288和4837168,本文引用以供参考)。例如,抗本发明多肽的标记的单克隆抗体可用于检测生物学样品中的裂殖子。作为选择,本发明标记的多肽可用于检测生物学样品中抗SABP或DABP抗体的存在。至于诊断性免疫试验中的一般方法,也见Basic and Clinical Immunology tth Edition(CD.Sti es and A.Terr edy)1991,本文引用以供参考。
另外,修饰的多肽,抗体或其它能抑制SABP或DABP与红细胞间相互作用的化合物可测定生物活性。例如,多肽可在细胞表面以重组形式进行表达且可按下面所述测定细胞结合红细胞的能力。作为选择,可试验肽或抗体抑制红细胞与裂殖子或SABP和DABP之间的结合的能力。
也可使用无细胞试验测定DABP和SABP多肽与分离的Duffy抗原或血型糖蛋白多肽的结合。例如,红细胞蛋白质可被固着于固体表面并可测定标记的SABP或DABP多肽的结合。
许多试验方法使用标记的试验成份。标记系统可以是各种形式。可根据本领域熟知的方法将标记物与试验所需的成份直接或间接偶联。可使用大范围的各种标记物。成份可用一些方法中的任意一种进行标记。最常用的检测方法是使用对3H,125I,35S,14C或32P标记的成份或类似物进行放射自显影。非放射活性标记包括与标记的抗体,荧光团,化学发光剂,酶和能用作标记配体的特异性结合对成员的抗体相结合的配体。标记的选择取决于所需的灵敏性,与化合物连接的容易程度,稳定性需要和可得到的仪器。
另外,本发明的多肽可使用本领域的技术人员熟知的动物模型来试验。用于镰状疟原虫的体内模型包括Aotus sp。猴或黑猩猩;用于间日疟原虫的体内模型Saimiri猴。
H.含有结合区多肽的药用组合物
本发明的多肽在治疗疟疾的治疗学和预防学应用中有用。本发明的药用组合物适用于各种药品传递系统。用于本发明的合适配方见Remington′s Pharmaceutical Sciences,Mack Publishing Company,Philadelphia,PA,17th ed.(1985),本文引用以供参考。至于药品传递方法的简要描述见Langer,Science 249:1527-1533(1990),本文引用以供参考。
本发明的多肽可以药用和疫苗组合物使用,它们在治疗哺乳动物,特别是人类中是有用的。多肽可在某些情况下一起施用(例如在很可能同时被镰状疟原虫和间日疟原虫感染的情况下)。因此,单个药用组合物就可用于或预防由两种疟原虫引起的疟疾。
组合物适用于一次施用或系列地施用。当以系列给药时,在起始用药后依次进行接种以加强免疫反应,典型地称为加强接种。
本发明的药用组合物打算用于肠胃外,局部,口服或定点用药。优选的是药用组合物经肠胃外施用,例如经静脉内,皮下,皮内或肌肉内用药。因此,本发明提供的经肠胃外施用的组合物包含上述试剂溶于或悬浮于一种可接受的载体(优选一种含水载体)中的溶液。可使用各种含水载体,例如,水,缓冲水,0.4%盐水,0.3%甘氨酸,透明质酸和类似物。这些组合物可用常规熟知的灭菌技术来灭菌或可过滤灭菌。所得水溶液可包装备用或经冻干。施用前将冻干制品与无溶液混合。按照挖近似生理条件的需要组合物可含药用上可接受的辅助物质,如pH调节和缓冲剂,张力调节剂,润湿剂和类似物。例如:醋酸钠、乳酸钠、氯化钠、氯化钾、氯化钙、山梨聚糖单月桂酸酯,三乙醇胺油酸酯等。
至于固态组合物,可使用常规无毒固态载体,例如包括药用级的甘露醇、乳糖、淀粉、硬脂酸镁、糖精钠、滑石、纤维素、葡萄糖、蔗糖、碳酸镁和类似物。对于口服用药,药用上可接受的无毒组合物经掺入任意一种通常使用的赋形剂(如前面列出的那些载体)和通常10-95%的活性成份(更优选25%-75%的浓度)来形成。
对于以烟雾剂进行的用药,优选使用以细小的分离形式与表面活性剂和推进剂一起的多肽。当然,表面活性剂必须是无毒的并优选可溶于推进剂。这种试剂的代表是酯或部分含6到22个碳原子的脂肪酸酯,如己酸、辛酸、月桂酸、软脂酸、硬脂酸、亚油酸、亚麻酸、olesteric和油酸的脂肪族多羟基醇酯或其环酐。可使用混合的酯,如混合的或天然的甘油酯。如果需要,也可包括一种载体,例如以鼻内用药时可含卵磷脂。
在一些实施例中,可用SABP或DABP多肽或其它特异性抑制(例如单克隆抗体)治疗疟疾病人以阻止疟原虫属裂殖子和裂殖体与红细胞表面的结合。
病人用药量的范围取决于施用何种药物,病人的状态和用药方式。在治疗应用中,给已患有疟疾的病人施用的组合物的量应足以抑制疟原虫通过红细胞的传播并因此治愈或至少部分控制该疾病和其并发症的症状。是以实现该目的的量定义为“治疗有效量”。对这一用途有效的量取决于疾病的严重性和病人的体重和一般状态。但一般范围是每天大约1mg到大约5gm,对于70kg的病人,优选大约100mg。
作为选择,本发明的多肽可在预防上用作疫苗。本发明的疫苗含作为有效成份的免疫有效量的结合区多肽或本文所述的重组病毒。免疫应答可包括抗体的产生,抗存在来自本发明SABP、DABP或EBL序列编码肽的多肽的细胞之细胞毒T淋巴细胞(CTL)的激活,或本领域已知的其它机制。例如见Paul Funp damental Immunology Second Edition Pub-lished by Roven press New York(本文引用以供参考)关于免疫应答的描述。有用的载体是本领域所熟知的,例如它们包括甲状腺球蛋白,诸如人血清白蛋白的白蛋白,破伤风类毒素。多聚氨基酸如聚(D-赖氨酸:D-谷氨酸),流感、肝炎B病毒核心蛋白质,肝炎B病毒重组疫苗。疫苗也可含有生理耐受性(可接受的)稀释剂,如水,磷酸盐缓冲液,或盐水,典型地还含有佐剂。诸如不完全Freund氏佐剂,磷酸铝,氢氧化铝,或明矾的佐剂是本领域熟知的物质。
编码SABP或DABP结合区和EBL基因家族基序的DNA或RNA可导入病人以获得对核酸编码的多肽的免疫应答。Wolff et,al.,Science 247:1465-1468(1990)(本文引用以供参考)描述了核酸在引起该核酸编码的基因表达中的使用。
含本发明的多肽,核酸或病毒的疫苗组合物施用给病人以诱导抗该多肽的保护性免疫应答。“保护性免疫应答”指阻止或抑制疟原虫通过红细胞的扩散,从而至少部分阻止该疾病和其并发疟的症状。是以达到这一目的的量定义的“免疫有效剂量”。在这一用途中有效的量取决于所用的组合物,用药方式,病人的体重和一般健康状态,以及处方医生的判断。对于多肽组合物,开始免疫的一般范围(治疗或预防用药)用于70kg的病人是从大约10μg到大约1gm的多肽,随后的加强剂量按照从几周到几月(取决于病人的反应和状态,例如,经测量病人血液中的疟原虫水平)的加强方式从大约100μg到大约1gm的多肽。对于核酸,典型地将30-1000μg的核酸注射入70kg的病人,接着如果合适就注射加强剂量。
下面以说明的方式而不是限制的方式提供实施例。
实施例
作为红细胞结合区的SABP和DABP
氨基末端,半胱氨酸富集区的鉴定
1.SABP结合区多肽在Cos细胞表面的表达
为了证实SABP蛋白质的氨基末端,半胱氨酸富集区是唾液酸结合区,在哺乳动物Cos细胞表面体外表达蛋白质的这一区域。这一DNA序列是SABP DNA序列(SEQ ID No3)上从位置1到位置1848。聚合酶链式反应技术(PCR)用于直接从克隆基因中扩增SABP DNA的这一区域。
将与Pvull或Apal的限制性内切酶位点相对应的序列掺入用于PCR扩增的寡核苻酸序列中以利于将PCR扩增区域插入pRE4载体中(见下面)。合成特异性的寡核苷酸5′-ATCGATCAGCTGGGAAGAAATACTTCATCT-3′。这些寡核甘酸用作PCR扩增编码SABP蛋白半胱氨酸富集的氨基末端区的DNA序列区的引物。
PCR条件以Saiki,et al.,Science 239:487-491(1988)描述的标准为基础。从经过剪接并以单个开架阅读框片段再克隆的编码SABP的基因克隆片段提供模板DNA。
用于在Cos细胞中表达的载体pRE4如图1所示。该载体有一个SV40复制起,一个氨苄青霉素抗性标记和在Rous肉瘤病毒长末端重复(RSV LTR)下游克隆的单纯疱疹病毒糖蛋白D基因(HSV glyd)。使用HSV glyd上的Pvull和Apal位点切除HSV glyd基因的部分细胞外区域。
如上面所述,PCR寡核苷酸引物含Pvull或Apal限制性位点,用限制性酶Pvull和Apal消化上面得到的PCR扩增的DNA片段并克隆到载体pRE4的Pvull和Apal位点上。设计这些构建体来表达以在N末端与HSV glyd信号序列及在C末端与HSV glyd跨膜和胞质区嵌合的蛋白质形式出现的SABP蛋白质区域。HSV glyd信号区将这些嵌合蛋白质定位于Cos细胞表面,HSV glyd跨膜片段将这些嵌合蛋白质锚着于Cos细胞表面。
根据标准技术以磷酸钙沉淀法用含PCR扩增的SABPDNA区域的pRE4构建体转染哺乳动物Cos细胞。
2.DABP结合区多肽在Cos细胞表面的表达
为了证实DABP蛋白质的氨基末端半胱氨酸富集区是结合区,在Cos细胞表面表达这一区域。首先从位置1-975经PCR扩增DNA序列的这一区域(SEQ ID NO.1)。
将与Pvull和Apal的限制性核酸内切酶位点相对应的序列掺入用于PCR扩增的寡核苷酸探针中。以利于随后将扩增的DNA插入pRE4载体中,如上所述。合成寡核苷酸5′-TCTCGTCAGCTGACGATCTCTAGTGCTATT-3′和5′-ACGAGTGGGCCCTGTCACAACTTCCTGAGT-3′。这些寡核苷酸用作引物,使用与上面所述相同的条件直接从克隆的DABP基因中扩增编码DABP蛋白质半胱氨酸富集的氨基末端区的DABP DNA序列区域。
也使用与上面在Cos细胞表达SABP区域部分中所述相同的pRE4载体作为DABP DNA区域的载体。
3.与红细胞的结合试验
为了证实它们与人红细胞结合的能力,将转染的表达DABP和SABP结合区的Cos细胞与红细胞在培养基(DMEM/10%FBS)中37℃下培养2小时。用磷酸盐缓冲液洗涤5次去掉未附着的红细胞用光学显微镜观察结合的细细胞。在其表面表达氨基末端半胱氨酸富集的SABP多肽的Cos细胞与未处理的人红细胞结合,但不与神经氨酸苷酶处理的红细胞(即在其表面缺乏唾液酸残基,资料未显示)结合。在其表面表达SABP蛋白质其它区域的Cos细胞不结合人红细胞(资料未显示)。这些结果将SABP的氨基末端半胱氨酸富集区鉴定为红细胞结合区,表明表达这些区域的Cos细胞与人红细胞的结合是特异性的。而且,表达区与红细胞的结合与在结合红细胞方面可信的SABP-175分子所见的结合方式相同。
同样地,在其表面表达DABP氨基末端半胱氨酸富集区的Cos细胞结合Duffy阳性人红细胞,但不结合Duffy阴性人红细胞(即缺乏Duffy血型抗原的红细胞,资料未显示)。在其表面表达DABP蛋白质其它区域的Cos细胞不结合人红细胞(资料未显示)。这些结果将DABP氨基末端半胱氨酸富集区鉴定为红细胞结合区并表明Cos细胞的结合是特异性的。
序列描述(1)一般资料:(I)申请人
(A)名称:美国,由健康和人类服务部秘书代表(II)发明题目:间日疟原虫和镰状疟原早红细胞结合蛋白
的结合区(III)序列数:l2(IV)计算机可读形式:
(A)媒体类型:Floppy盘
(B)计算机:IBM PC兼容性
(C)操作系统:PC-DOS/MS-DOS
(D)软件:Patent In Realease#1.0,Version#1.25(V)最近申请资料:
(A)申请号:WO尚未脂定
(B)申请日:1994年9月7日
(C)分类:(VI)优先权申请资料:
(A)申请号:US 08/119,677
(B)申请日:1993年9月10日(VII)代理人/代理资料:
(A)姓名:Bastian,Kevin L.
(B)登记号:34,774
(C)参考/摘要号:15280-139000(VIII)电信资料
(A)电话:(415)543-9600
(B)电传:(415)543-5043(2)GEQ ID NO:1资料:(I)序列特征:
(A)长度:4084碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:DNA(基因组)(III)假定:非(VI)原始来源:
(A)生物:间日疟原虫(XI)序列描述:SEA ID NO:1:AAGCTTTTAA AAATAGCAAC AAAATTTCGA AACATTGCCA CAAAAATTTT ATGTTTTACA 60TATATTTAGA TTCATACAAT TTAGGTGTAC CCTGTTTTTT GATATATGCG CTTAAATTTT 120TTTTTCGCTC ATATGTTTAG TTATATGTGT AGAACAACTT GCTGAATAAA TTACGTACAC 180TTTCTGTTCT GAATAATATT ACCACATACA TTTAATTTTA AATACTATGA AAGGAAAAAA 240CCGCTCTTTA TTTGTTCTCC TAGTTTTATT ATTGTTACAC AAGGTATCAT ATAAGGATGA 300TTTTTCTATC ACACTAATAA ATTATCATGA AGGAAAAAAA TATTTAATTA TACTAAAAAG 360AAAATTAGAA AAAGCTAATA ATCGTGATGT TTGCAATTTT TTTCTTCATT TCTCTCAGGT 420AAATAATGTA TTATTAGAAC GAACAATTGA AACCCTTCTA GAATGCAAAA ATGAATATGT 480GAAAGGTGAA AATGGTTATA AATTAGCTAA AGGACACCAC TGTGTTGAGG AAGATAACTT 540AGAACGATGG TTACAAGGAA CCAATGAAAG AAGAAGTGAG GAAAATATAA AATATAAATA 600TGGAGTAACG GAACTAAAAA TAAAGTATGC GCAAATGAAT GGAAAAAGAA GCAGCCGCAT 660TTTGAAGGAA TCAATTTACG GGGCGCATAA CTTTGGAGGC AACAGTTACA TGGAGGGAAA 720AGATGGAGGA GATAAAACTG GGGAGGAAAA AGATGGAGAA CATAAAACTG ATAGTAAAAC 780TGATAACGGG AAAGGTGCAA ACAATTTGGT AATGTTAGAT TATGAGACAT CTAGCAATGG 840CCAGCCAGCG GGAACCCTTG ATAATGTTCT TGAATTTGTG ACTGGGCATG AGGGAAATTC 900TCGTAAAAAT TCCTCGAATG GTGGCAATCC TTACGATATT GATCATAAGA AAACGATCTC 960TAGTGCTATT ATAAATCATG CTTTTCTTCA AAATACTGTA ATGAAAAACT GTAATTATAA 1020GAGAAAACGT CGGGAAAGAG ATTGGGACTG TAACACTAAG AAGGATGTTT GTATACCAGA 1080TCGAAGATAT CAATTATGTA TGAAGGAACT TACGAATTTG GTAAATAATA CAGACACAAA 1140TTTTCATAGG GATATAACAT TTCGAAAATT ATATTTGAAA AGGAAACTTA TTTATGATGC 1200TGCAGTAGAG GGCGATTTAT TACTTAAGTT GAATAACTAC AGATATAACA AAGACTTTTG 1260CAAGGATATA AGATGGAGTT TGGGAGATTT TGGAGATATA ATTATGGGAA CGGATATGGA 1320AGGCATCGGA TATTCCAAAG TAGTGGAAAA TAATTTGCGC AGCATCTTTG GAACTGATGA 1380AAAGGCCCAA CAGCGTCGTA AACAGTGGTG GAATGAATCT AAAGCACAAA TTTGGACAGC 1440AATGATGTAC TCAGTTAAAA AAAGATTAAA GGGGAATTTT ATATGGATTT GTAAATTAAA 1500TGTTGCGGTA AATATAGAAC CGCAGATATA TAGATGGATT CGAGAATGGG GAAGGGATTA 1560CGTGTCAGAA TTGCCCACAG AAGTGCAAAA ACTGAAAGAA AAATGTGATG GAAAAATCAA 1620TTATACTGAT AAAAAAGTAT GTAAGGTACC ACCATGTCAA AATGCGTGTA AATCATATGA 1680TCAATGGATA ACCAGAAAAA AAAATCAATG GGATGTTCTG TCAAATAAAT TCATAAGTGT 1740AAAAAACGCA GAAAAGGTTC AGACGGCAGG TATCGTAACT CCTTATGATA TACTAAAACA 1800GGAGTTAGAT GAATTTAACG AGGTGGCTTT TGAGAATGAA ATTAACAAAC GTGATGGTGC 1860ATATATTGAG TTATGCGTTT GTTCCGTTGA AGAGGCTAAA AAAAATACTC AGGAAGTTGT 1920GACAAATGTG GACAATGCTG CTAAATCTCA GGCCACCAAT TCAAATCCGA TAAGTCAGCC 1980TGTAGATAGT AGTAAAGCGG AGAAGGTTCC AGGAGATTCT ACGCATGGAA ATGTTAACAG 2040TGGCCAAGAT AGTTCTACCA CAGGTAAAGC TGTTACGGGG GATGGTCAAA ATGGAAATCA 2100GACACCTGCA GAAAGCGATG TACAGCGAAG TGATATTGCC GAAAGTGTAA GTGCTAAAAA 2160TGTTGATCCG CAGAAATCTG TAAGTAAAAG AAGTGACGAC ACTGCAAGCG TTACAGGTAT 2220TGCCGAAGCT GGAAAGGAAA ACTTAGGCGC ATCAAATAGT CGACCTTCTG AGTCCACCGT 2280TGAAGCAAAT AGCCCAGGTG ATGATACTGT GAACAGTGCA TCTATACCTG TAGTGAGTGG 2340TGAAAACCCA TTGGTAACCC CCTATAATGG TTTGAGGCAT TCGAAAGACA ATAGTGATAG 2400CGATGGACCT GCGGAATCAA TGGCGAATCC TGATTCAAAT AGTAAAGGTG AGACGGGAAA 2460GGGGCAAGAT AATGATATGG CGAAGGCTAC TAAAGATAGT AGTAATAGTT CAGATGGTAC 2520CAGCTCTGCT ACGGGTGATA CTACTGATGC AGTTGATAGG GAAATTAATA AAGGTGTTCC 2580TGAGGATAGG GATAAAACTG TAGGAAGTAA AGATGGAGGG GGGGAAGATA ACTCTGCAAA 2640TAAGGATGCA GCGACTGTAG TTGGTGAGGA TAGAATTCGT GAGAACAGCG CTGGTGGTAG 2700CACTAATGAT AGATCAAAAA ATGACACGGA AAAGAACGGG GCCTCTACCC CTGACAGTAA 2760ACAAAGTGAG GATGCAACTG CGCTAAGTAA AACCGAAAGT TTAGAATCAA CAGAAAGTGG 2820AGATAGAACT ACTAATGATA CAACTAACAG TTTAGAAAAT AAAAATGGAG GAAAAGAAAA 2880GGATTTACAA AAGCATGATT TTAAAAGTAA TGATACGCCG AATGAAGAAC CAAATTCTGA 2940TCAAACTACA GATGCAGAAG GACATGACAG GGATAGCATC AAAAATGATA AAGCAGAAAG 3000GAGAAAGCAT ATGAATAAAG ATACTTTTAC GAAAAATACA AATAGTCACC ATTTAAATAG 3060TAATAATAAT TTGAGTAATG GAAAATTAGA TATAAAAGAA TACAAATACA GAGATGTCAA 3120AGCAACAAGG GAAGATATTA TATTAATGTC TTCAGTACGC AAGTGCAACA ATAATATTTC 3180TTTAGAGTAC TGTAACTCTG TAGAGGACAA AATATCATCG AATACTTGTT CTAGAGAGAA 3240AAGTAAAAAT TTATGTTGCT CAATATCGGA TTTTTGTTTG AACTATTTTG ACGTGTATTC 3300TTATGAGTAT CTTAGCTGCA TGAAAAAGGA ATTTGAAGAT CCATCCTACA AGTGCTTTAC 3360GAAAGGGGGC TTTAAAGGTA TGCAGAAAAA GATGCTGAAT AGAGAAAGGT GTTGAGTAAA 3420TTAAAAAGGA ATTAATTTTA GGAATGTTAT AAACATTTTT GTACCCAAAA TTCTTTTTGC 3480AGACAAGACT TACTTTGCCG CGGCGGGAGC GTTGCTGATA CTGCTGTTGT TAATTGCTTC 3540AAGGAAGATG ATCAAAAATG AGTAACCAGA AAATAAAATA AAATAACATA AAATAAAATA 3600AAAACTAGAA TAACAATTAA AATAAAATAA AATGAGAAAT GCCTGTTAAT GCACAGTTAA 3660TTCTAACGAT TCCATTTGTG AAGTTTTAAA GAGAGCACAA ATGCATAGTC ATTATGTCCA 3720TGCATATATA CACATATATG TACGTATATA TAATAAACGC ACACTTTCTT GTTCGTACAG 3780TTCTGAAGAA GCTACATTTA ATGAGTTTGA AGAATACTGT GATAATATTC ACAGAATCCC 3840TCTGATGCCT AACAGTAATT CAAATTTCAA GAGCAAAATT CCATTTAAAA AGAAATGTTA 3900CATCATTTTG CGTTTTTCTT TTTTTCTTTT TTTTTTCTTT TTTAGATATT GAACACATGC 3960AGCCATCAAC CCCCCTGGAT TATTCATGAT GCTACTTTGG TAAGTAAAAG CAATTCTGAT 4020TGTAGTGCTG ATGTAATTTT AGTCATTTTG CTTGCTGCAA TAAACGAGAA AATATATCAA 4080GCTT 4084(2)SEQ ID NO:2资料:(I)序列特征:
(A)长度:1115氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:蛋白质(III)假定的:非(VI)原始来源:
(A)生物:间日疟原虫(XI)序列描述:SEA ID NO:2:Met Lys Gly Lys Asn Arg Ser Leu Phe Val Leu Leu Val Leu Leu Leu1 5 10 15Leu His Lys Val Ser Tyr Lys Asp Asp Phe Ser Ile Thr Leu Ile Asn
20 25 30Tyr His Glu Gly Lys Lys Tyr Leu Ile Ile Leu Lys Arg Lys Leu Glu
35 40 45Lys Ala Asn Asn Arg Asp Val Cys Asn Phe Phe Leu His Phe Ser Gln
50 55 60Val Asn Asn Val Leu Leu Glu Arg Thr Ile Glu Thr Leu Leu Glu Cys65 70 75 80Lys Asn Glu Tyr Val Lys Gly Glu Asn Gly Tyr Lys Leu Ala Lys Gly
85 90 95His His Cys Val Glu Glu Asp Asn Leu Glu Arg Trp Leu Gln Gly Thr
100 105 110Asn Glu Arg Arg Ser Glu Glu Asn Ile Lys Tyr Lys Tyr Gly Val Thr
115 120 125Glu Leu Lys Ile Lys Tyr Ala Gln Met Asn Gly Lys Arg Ser Ser Arg
130 135 140Ile Leu Lys Glu Ser Ile Tyr Gly Ala His Asn Phe Gly Gly Asn Ser145 150 155 160Tyr Met Glu Gly Lys Asp Gly Gly Asp Lys Thr Gly Glu Glu Lys Asp
165 170 175Gly Glu His Lys Thr Asp Ser Lys Thr Asp Asn Gly Lys Gly Ala Asn
180 185 190Asn Leu Val Met Leu Asp Tyr Glu Thr Ser Ser Asn Gly Gln Pro Ala
195 200 205Gly Thr Leu Asp Asn Val Leu Glu Phe Val Thr Gly His Glu Gly Asn
210 215 220Ser Arg Lys Asn Ser Ser Asn Gly Gly Asn Pro Tyr Asp Ile Asp His225 230 235 240Lys Lys Thr Ile Ser Ser Ala Ile Ile Asn His Ala Phe Leu Gln Asn
245 250 255Thr Val Met Lys Asn Cys Asn Tyr Lys Arg Lys Arg Arg Glu Arg Asp
260 265 270Trp Asp Cys Asn Thr Lys Lys Asp Val Cys Ile Pro Asp Arg Arg Tyr
275 280 285Gln Leu Cys Met Lys Glu Leu Thr Asn Leu Val Asn Asn Thr Asp Thr
290 295 300Asn Phe His Arg Asp Ile Thr Phe Arg Lys Leu Tyr Leu Lys Arg Lys305 310 315 320Leu Ile Tyr Asp Ala Ala Val Glu Gly Asp Leu Leu Leu Lys Leu Asn
325 330 335Asn Tyr Arg Tyr Asn Lys Asp Phe Cys Lys Asp Ile Arg Trp Ser Leu
340 345 350Gly Asp Phe Gly Asp Ile Ile Met Gly Thr Asp Met Glu Gly Ile Gly
355 360 365Tyr Ser Lys Val Val Glu Asn Asn Leu Arg Ser Ile Phe Gly Thr Asp
370 375 380Glu Lys Ala Gln Gln Arg Arg Lys Gln Trp Trp Asn Glu Ser Lys Ala385 390 395 400Gln Ile Trp Thr Ala Met Met Tyr Ser Val Lys Lys Arg Leu Lys Gly
405 410 415Asn Phe Ile Trp Ile Cys Lys Leu Asn Val Ala Val Asn Ile Glu Pro
420 425 430Gln Ile Tyr Arg Trp Ile Arg Glu Trp Gly Arg Asp Tyr Val Ser Glu
435 440 445Leu Pro Thr Glu Val Gln Lys Leu Lys Glu Lys Cys Asp Gly Lys Ile
450 455 460Asn Tyr Thr Asp Lys Lys Val Cys Lys Val Pro Pro Cys Gln Asn Ala465 470 475 480Cys Lys Ser Tyr Asp Gln Trp Ile Thr Arg Lys Lys Asn Gln Trp Asp
485 490 495Val Leu Ser Asn Lys Phe Ile Ser Val Lys Asn Ala Glu Lys Val Gln
500 505 510Thr Ala Gly Ile Val Thr Pro Tyr Asp Ile Leu Lys Gln Glu Leu Asp
515 520 525Glu Phe Asn Glu Val Ala Phe Glu Asn Glu Ile Asn Lys Arg Asp Gly
530 535 540Ala Tyr Ile Glu Leu Cys Val Cys Ser Val Glu Glu Ala Lys Lys Asn545 550 555 560Thr Gln Glu Val Val Thr Asn Val Asp Asn Ala Ala Lys Ser Gln Ala
565 570 575Thr Asn Ser Asn Pro Ile Ser Gln Pro Val Asp Ser Ser Lys Ala Glu
580 585 590Lys Val Pro Gly Asp Ser Thr His Gly Asn Val Asn Ser Gly Gln Asp
595 600 605Ser Ser Thr Thr Gly Lys Ala Val Thr Gly Asp Gly Gln Asn Gly Asn
610 615 620Gln Thr Pro Ala Glu Ser Asp Val Gln Arg Ser Asp Ile Ala Glu Ser625 630 635 640Val Ser Ala Lys Asn Val Asp Pro Gln Lys Ser Val Ser Lys Arg Ser
645 650 655Asp Asp Thr Ala Ser Val Thr Gly Ile Ala Glu Ala Gly Lys Glu Asn
660 665 670Leu Gly Ala Ser Asn Ser Arg Pro Ser Glu Ser Thr Val Glu Ala Asn
675 680 685Ser Pro Gly Asp Asp Thr Val Asn Ser Ala Ser Ile Pro Val Val Ser
690 695 700Gly Glu Asn Pro Leu Val Thr Pro Tyr Asn Gly Leu Arg His Ser Lys705 710 715 720Asp Asn Ser Asp Ser Asp Gly Pro Ala Glu Ser Met Ala Asn Pro Asp
725 730 735Ser Asn Ser Lys Gly Glu Thr Gly Lys Gly Gln Asp Asn Asp Met Ala
740 745 750Lys Ala Thr Lys Asp Ser Ser Asn Ser Ser Asp Gly Thr Ser Ser Ala
755 760 765Thr Gly Asp Thr Thr Asp Ala Val Asp Arg Glu Ile Asn Lys Gly Val
770 775 780Pro Glu Asp Arg Asp Lys Thr Val Gly Ser Lys Asp Gly Gly Gly Glu785 790 795 800Asp Asn Ser Ala Asn Lys Asp Ala Ala Thr Val Val Gly Glu Asp Arg
805 810 815Ile Arg Glu Asn Ser Ala Gly Gly Ser Thr Asn Asp Arg Ser Lys Asn
820 825 830Asp Thr Glu Lys Asn Gly Ala Ser Thr Pro Asp Ser Lys Gln Ser Glu
835 840 845Asp Ala Thr Ala Leu Ser Lys Thr Glu Ser Leu Glu Ser Thr Glu Ser
850 855 860Gly Asp Arg Thr Thr Asn Asp Thr Thr Asn Ser Leu Glu Asn Lys Asn865 870 875 880Gly Gly Lys Glu Lys Asp Leu Gln Lys His Asp Phe Lys Ser Asn Asp
885 890 895Thr Pro Asn Glu Glu Pro Asn Ser Asp Gln Thr Thr Asp Ala Glu Gly
900 905 910His Asp Arg Asp Ser Ile Lys Asn Asp Lys Ala Glu Arg Arg Lys His
915 920 925Met Asn Lys Asp Thr Phe Thr Lys Asn Thr Asn Ser His His Leu Asn
930 935 940Ser Asn Asn Asn Leu Ser Asn Gly Lys Leu Asp Ile Lys Glu Tyr Lys945 950 955 960Tyr Arg Asp Val Lys Ala Thr Arg Glu Asp Ile Ile Leu Met Ser Ser
965 970 975Val Arg Lys Cys Asn Asn Asn Ile Ser Leu Glu Tyr Cys Asn Ser Val
980 985 990Glu Asp Lys Ile Ser Ser Asn Thr Cys Ser Arg Glu Lys Ser Lys Asn
995 1000 1005Leu Cys Cys Ser Ile Ser Asp Phe Cys Leu Asn Tyr Phe Asp Val Tyr
1010 1015 1020Ser Tyr Glu Tyr Leu Ser Cys Met Lys Lys Glu Phe Glu Asp Pro Ser1025 1030 1035 1040Tyr Lys Cys Phe Thr Lys Gly Gly Phe Lys Ile Asp Lys Thr Tyr Phe
1045 1050 1055Ala Ala Ala Gly Ala Leu Leu Ile Leu Leu Leu Ile Ala Ser Arg Lys
1060 1065 1070Met Ile Lys Asn Asp Ser Glu Glu Ala Thr Phe Asn Glu Phe Glu Glu
1075 1080 1085Tyr Cys Asp Asn Ile His Arg Ile Pro Leu Met Pro Asn Asn Ile Glu
1090 1095 1100His Met Gln Pro Ser Thr Pro Leu Asp Tyr Ser1105 1110 1115(2)SEQ ID NO:3资料:(I)序列特征:
(A)长度:4507碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:DNA(基因组)(III)假定的:非(VI)原始来源:
(A)生物:镰状疟原虫(XI)序列描述:SEA ID NO:3:TATATATATA TATATATATA GATAATAACA TATAAATATA TTCAATGTGC ATACAATGAA 60ATGTAATATT AGTATATATT TTTTTGCTTC CTTCTTTGTG TTATATTTTG CAAAAGCTAG 120GAATGAATAT GATATAAAAG AGAATGAAAA ATTTTTAGAC GTGTATAAAG AAAAATTTAA 180TGAATTAGAT AAAAAGAAAT ATGGAAATGT TCAAAAAACT GATAAGAAAA TATTTACTTT 240TATAGAAAAT AAATTAGATA TTTTAAATAA TTCAAAATTT AATAAAAGAT GGAAGAGTTA 300TGGAACTCCA GATAATATAG ATAAAAATAT GTCTTTAATA AATAAACATA ATAATGAAGA 360AATGTTTAAC AACAATTATC AATCATTTTT ATCGACAAGT TCATTAATAA AGCAAAATAA 420ATATGTTCCT ATTAACGCTG TACGTGTGTC TAGGATATTA AGTTTCCTGG ATTCTAGAAT 480TAATAATGGA AGAAATACTT CATCTAATAA CGAAGTTTTA AGTAATTGTA GGGAAAAAAG 540GAAAGGAATG AAATGGGATT GTAAAAAGAA AAATGATAGA AGCAACTATG TATGTATTCC 600TGATCGTAGA ATCCAATTAT GCATTGTTAA TCTTAGCATT ATTAAAACAT ATACAAAAGA 660GACCATGAAG GATCATTTCA TTGAAGCCTC TAAAAAAGAA TCTCAACTTT TGCTTAAAAA 720AAATGATAAC AAATATAATT CTAAATTTTG TAATGATTTG AAGAATAGTT TTTTAGATTA 780TGGACATCTT GCTATGGGAA ATGATATGGA TTTTGGAGGT TATTCAACTA AGGCAGAAAA 840CAAAATTCAA GAAGTTTTTA AAGGGGCTCA TGGGGAAATA AGTGAACATA AAATTAAAAA 900TTTTAGAAAA GAATGGTGGA ATGAATTTAG AGAGAAACTT TGGGAAGCTA TGTTATCTGA 960GCATAAAAAT AATATAAATA ATTGTAAAAA TATTCCCCAA GAAGAATTAC AAATTACTCA 1020ATGGATAAAA GAATGGCATG GAGAATTTTT GCTTGAAAGA GATAATAGAT CAAAATTGCC 1080AAAAAGTAAA TGTAAAAATA ATACATTATA TGAAGCATGT GAGAAGGAAT GTATTGATCC 1140ATGTATGAAA TATAGAGATT GGATTATTAG AAGTAAATTT GAATGGCATA CGTTATCGAA 1200AGAATATGAA ACTCAAAAAG TTCCAAAGGA AAATGCGGAA AATTATTTAA TCAAAATTTC 1260AGAAAACAAG AATGATGCTA AAGTAAGTTT ATTATTGAAT AATTGTGATG CTGAATATTC 1320AAAATATTGT GATTGTAAAC ATACTACTAC TCTCGTTAAA AGCGTTTTAA ATGGTAACGA 1380CAATACAATT AAGGAAAAGC GTGAACATAT TGATTTAGAT GATTTTTCTA AATTTGGATG 1440TGATAAAAAT TCCGTTGATA CAAACACAAA GGTGTGGGAA TGTAAAAACC CTTATATATT 1500ATCCACTAAA GATGTATGTG TACCTCCGAG GAGGCAAGAA TTATGTCTTG GAAACATTGA 1560TAGAATATAC GATAAAAACC TATTAATGAT AAAAGAGCAT ATTCTTGCTA TTGCAATATA 1620TGAATCAAGA ATATTGAAAC GAAAATATAA GAATAAAGAT GATAAAGAAG TTTGTAAAAT 1680CATAAATAAA ACTTTCGCTG ATATAAGAGA TATTATAGGA GGTACTGATT ATTGGAATGA 1740TTTGAGCAAT AGAAAATTAG TAGGAAAAAT TAACACAAAT TCAAAATATG TTCACAGGAA 1800TAAAAAAAAT GATAAGCTTT TTCGTGATGA GTGGTGGAAA GTTATTAAAA AAGATGTATG 1860GAATGTGATA TCATGGGTAT TCAAGGATAA AACTGTTTGT AAAGAAGATG ATATTGAAAA 1920TATACCACAA TTCTTCAGAT GGTTTAGTGA ATGGGGTGAT GATTATTGCC AGGATAAAAC 1980AAAAATGATA GAGACTCTGA AGGTTGAATG CAAAGAAAAA CCTTGTGAAG ATGACAATTG 2040TAAAAGTAAA TGTAATTCAT ATAAAGAATG GATATCAAAA AAAAAAGAAG AGTATAATAA 2100ACAAGCCAAA CAATACCAAG AATATCAAAA AGGAAATAAT TACAAAATGT ATTCTGAATT 2160TAAATCTATA AAACCAGAAG TTTATTTAAA GAAATACTCG GAAAAATGTT CTAACCTAAA 2220TTTCGAAGAT GAATTTAAGG AAGAATTACA TTCAGATTAT AAAAATAAAT GTACGATGTG 2280TCCAGAAGTA AAGGATGTAC CAATTTCTAT AATAAGAAAT AATGAACAAA CTTCGCAAGA 2340AGCAGTTCCT GAGGAAAACA CTGAAATAGC ACACAGAACG GAAACTCCAT CTATCTCTGA 2400AGGACCAAAA GGAAATGAAC AAAAAGAACG TGATGACGAT AGTTTGAGTA AAATAAGTGT 2460ATCACCAGAA AATTCAAGAC CTGAAACTGA TGCTAAAGAT ACTTCTAACT TGTTAAAATT 2520AAAAGGAGAT GTTGATATTA GTATGCCTAA AGCAGTTATT GGGAGCAGTC CTAATGATAA 2580TATAAATGTT ACTGAACAAG GGGATAATAT TTCCGGGGTG AATTCTAAAC CTTTATCTGA 2640TGATGTACGT CCAGATAAAA AGGAATTAGA AGATCAAAAT AGTGATGAAT CGGAAGAAAC 2700TGTAGTAAAT CATATATCAA AAAGTCCATC TATAAATAAT GGAGATGATT CAGGCAGTGG 2760AAGTGCAACA GTGAGTGAAT CTAGTAGTTC AAATACTGGA TTGTCTATTG ATGATGATAG 2820AAATGGTGAT ACATTTGTTC GAACACAAGA TACAGCAAAT ACTGAAGATG TTATTAGAAA 2880AGAAAATGCT GACAAGGATG AAGATGAAAA AGGCGCAGAT GAAGAAAGAC ATAGTACTTC 2940TGAAAGCTTA AGTTCACCTG AAGAAAAAAT GTTAACTGAT AATGAAGGAG GAAATAGTTT 3000AAATCATGAA GAGGTGAAAG AACATACTAG TAATTCTGAT AATGTTCAAC AGTCTGGAGG 3060AATTGTTAAT ATGAATGTTG AGAAAGAACT AAAAGATACT TTAGAAAATC CTTCTAGTAG 3120CTTGGATGAA GGAAAAGCAC ATGAAGAATT ATCAGAACCA AATCTAAGCA GTGACCAAGA 3180TATGTCTAAT ACACCTGGAC CTTTGGATAA CACCAGTGAA GAAACTACAG AAAGAATTAG 3240TAATAATGAA TATAAAGTTA ACGAGAGGGA AGATGAGAGA ACGCTTACTA AGGAATATGA 3300AGATATTGTT TTGAAAAGTC ATATGAATAG AGAATCAGAC GATGGTGAAT TATATGACGA 3360AAATTCAGAC TTATCTACTG TAAATGATGA ATCAGAAGAC GCTGAAGCAA AAATGAAAGG 3420AAATGATACA TCTGAAATGT CGCATAATAG TAGTCAACAT ATTGAGAGTG ATCAACAGAA 3480AAACGATATG AAAACTGTTG GTGATTTGGG AACCACACAT GTACAAAACG AAATTAGTGT 3540TCCTGTTACA GGAGAAATTG ATGAAAAATT AAGGGAAAGT AAAGAATCAA AAATTCATAA 3600GGCTGAAGAG GAAAGATTAA GTCATACAGA TATACATAAA ATTAATCCTG AAGATAGAAA 3660TAGTAATACA TTACATTTAA AAGATATAAG AAATGAGGAA AACGAAAGAC ACTTAACTAA 3720TCAAAACATT AATATTAGTC AAGAAAGGGA TTTGCAAAAA CATGGATTCC ATACCATGAA 3780TAATCTACAT GGAGATGGAG TTTCCGAAAG AAGTCAAATT AATCATAGTC ATCATGGAAA 3840CAGACAAGAT CGGGGGGGAA ATTCTGGGAA TGTTTTAAAT ATGAGATCTA ATAATAATAA 3900TTTTAATAAT ATTCCAAGTA GATATAATTT ATATGATAAA AAATTAGATT TAGATCTTTA 3960TGAAAACAGA AATGATAGTA CAACAAAAGA ATTAATAAAG AAATTAGCAG AAATAAATAA 4020ATGTGAGAAC GAAATTTCTG TAAAATATTG TGACCATATG ATTCATGAAG AAATCCCATT 4080AAAAACATGC ACTAAAGAAA AAACAAGAAA TCTGTGTTGT GCAGTATCAG ATTACTGTAT 4140GAGCTATTTT ACATATGATT CAGAGGAATA TTATAATTGT ACGAAAAGGG AATTTGATGA 4200TCCATCTTAT ACATGTTTCA GAAAGGAGGC TTTTTCAAGT ATGATATTCA AATTTTTAAT 4260AACAAATAAA ATATATTATT ATTTTTATAC TTACAAAACT GCAAAAGTAA CAATAAAAAA 4320AATTAATTTC TCATTAATTT TTTTTTTCTT TTTTTCTTTT TAGGTATGCC ATATTATGCA 4380GGAGCAGGTG TGTTATTTAT TATATTGGTT ATTTTAGGTG CTTCACAAGC CAAATATCAA 4440AGGTTAGAAA AAATAAATAA AAATAAAATT GAGAAGAATG TAAATTAAAT ATAGAATTCG 4500AGCTCGG 4507(2)SEQ ID NO:4资料:(I)序列特征:
(A)长度:1426个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:蛋白质(III)假定的:非(VI)原始来源:
(A)生物:镰状疟原虫(XI)序列描述:SEA ID NO:4:Met Lys Cys Asn Ile Ser Ile Tyr Phe Phe Ala Ser Phe Phe Val Leu1 5 10 15Tyr Phe Ala Lys Ala Arg Asn Glu Tyr Asp Ile Lys Glu Asn Glu Lys
20 25 30Phe Leu Asp Val Tyr Lys Glu Lys Phe Asn Glu Leu Asp Lys Lys Lys
35 40 45Tyr Gly Asn Val Gln Lys Thr Asp Lys Lys Ile Phe Thr Phe Ile Glu
50 55 60Asn Lys Leu Asp Ile Leu Asn Asn Ser Lys Phe Asn Lys Arg Trp Lys65 70 75 80Ser Tyr Gly Thr Pro Asp Asn Ile Asp Lys Asn Met Ser Leu Ile Asn
85 90 95Lys His Asn Asn Glu Glu Met Phe Asn Asn Asn Tyr Gln Ser Phe Leu
100 105 110Ser Thr Ser Ser Leu Ile Lys Gln Asn Lys Tyr Val Pro Ile Asn Ala
115 120 125Val Arg Val Ser Arg Ile Leu Ser Phe Leu Asp Ser Arg Ile Asn Asn
130 135 140Gly Arg Asn Thr Ser Ser Asn Asn Glu Val Leu Ser Asn Cys Arg Glu145 150 155 160Lys Arg Lys Gly Met Lys Trp Asp Cys Lys Lys Lys Asn Asp Arg Ser
165 170 175Asn Tyr Val Cys Ile Pro Asp Arg Arg Ile Gln Leu Cys Ile Val Asn
180 185 190Leu Ser Ile Ile Lys Thr Tyr Thr Lys Glu Thr Met Lys Asp His Phe
195 200 205Ile Glu Ala Ser Lys Lys Glu Ser Gln Leu Phe Ser Leu Lys Asn Asp
210 215 220Asn Lys Tyr Asn Ser Lys Phe Cys Asn Asp Leu Lys Asn Ser Phe Leu225 230 235 240Asp Tyr Gly His Leu Ala Met Gly Asn Asp Met Asp Phe Gly Gly Tyr
245 250 255Ser Thr Lys Ala Glu Asn Lys Ile Gln Glu Val Phe Lys Gly Ala His
260 265 270Gly Glu Ile Set Glu His Lys Ile Lys Asn Phe Arg Lys Glu Trp Trp
275 280 285Asn Glu Phe Arg Glu Lys Leu Trp Glu Ala Met Leu Ser Glu His Lys
290 295 300Asn Asn Ile Asn Asn Cys Lys Asn Ile Ser Gln Glu Glu Leu Gln Ile305 310 315 320Thr Gln Trp Ile Lys Glu Trp His Gly Glu Phe Leu Leu Glu Arg Asp
325 330 335Asn Arg Ser Lys Leu Pro Lys Ser Lys Cys Lys Asn Asn Thr Leu Tyr
340 345 350Glu Ala Cys Glu Lys Glu Cys Ile Asp Pro Cys Met Lys Tyr Arg Asp
355 360 365Trp Ile Ile Arg Ser Lys Phe Glu Trp His Thr Leu Ser Lys Glu Tyr
370 375 380Glu Thr Gln Lys Val Pro Lys Glu Asn Ala Glu Asn Tyr Leu Ile Lys385 390 395 400Ile Ser Glu Asn Lys Asn Asp Ala Lys Val Ser Leu Leu Leu Asn Asn
405 410 415Cys Asp Ala Glu Tyr Ser Lys Tyr Cys Asp Cys Lys His Thr Thr Thr
420 425 430Leu Val Lys Ser Val Leu Asn Gly Asn Asp Asn Thr Ile Lys Glu Lys
435 440 445Arg Glu His Ile Asp Leu Asp Asp Phe Ser Lys Phe Gly Cys Asp Lys
450 455 460Asn Ser Val Asp Thr Asn Thr Lys Val Trp Glu Cys Lys Asn Pro Tyr465 470 475 480Ile Leu Ser Thr Lys Asp Val Cys Val Pro Pro Arg Arg Gln Glu Leu
485 490 495Cys Leu Gly Asn Ile Asp Arg Ile Tyr Asp Lys Asn Leu Leu Met Ile
500 505 510Lys Glu His Ile Leu Ala Ile Ala Ile Tyr Glu Ser Arg Ile Leu Lys
515 520 525Arg Lys Tyr Lys Asn Lys Asp Asp Lys Glu Val Cys Lys Ile Ile Asn
530 535 540Lys Thr Phe Ala Asp Ile Arg Asp Ile Ile Gly Gly Thr Asp Tyr Trp545 550 555 560Asn Asp Leu Ser Asn Arg Lys Leu Val Gly Lys Ile Asn Thr Asn Ser
565 570 575Lys Tyr Val His Arg Asn Lys Lys Asn Asp Lys Leu Phe Arg Asp Glu
580 585 590Trp Trp Lys Val Ile Lys Lys Asp Val Trp Asn VAl Ile Ser Trp Val
595 600 605Phe Lys Asp Lys Thr Val Cys Lys Glu Asp Asp Ile Glu Asn Ile Pro
610 615 620Gln Phe Phe Arg Trp Phe Ser Glu Trp Gly Asp Asp Tyr Cys Gln Asp625 630 635 640Lys Thr Lys Met Ile Glu Thr Leu Lys Val Glu Cys Lys Glu Lys Pro
645 650 655Cys Glu Asp Asp Asn Cys Lys Ser Lys Cys Asn Ser Tyr Lys Glu Trp
660 665 670Ile Ser Lys Lys Lys Lys Ser Ile Ile Thr Ser Asn Ile Pro Arg Ile
675 680 685Ser Lys Arg Asn Asn Tyr Lys Met Tyr Ser Glu Phe Lys Ser Ile Lys
690 695 700Pro Glu Val Tyr Leu Lys Lys Tyr Ser Lys Cys Ser Asn Leu Asn Phe705 710 715 720Glu Asp Glu Phe Lys Glu Glu Leu His Ser Asp Tyr Lys Asn Lys Cys
725 730 735Thr Met Cys Pro Glu Val Lys Asp Val Pro Ile Ser Ile Ile Arg Asn
740 745 750Asn Glu Gln Thr Ser Gln Glu Ala Val Pro Glu Glu Asn Thr Glu Ile
755 760 765Ala His Arg Thr Glu Thr Pro Ser Ile Ser Glu Gly Pro Lys Gly Asn
770 775 780Glu Gln Lys Glu Arg Asp Asp Asp Ser Leu Ser Lys Ile Ser Val Ser785 790 795 800Pro Glu Asn Ser Arg Pro Glu Thr Asp Ala Lys Asp Thr Ser Asn Leu
805 810 815Leu Lys Leu Lys Gly Asp Val Asp Ile Ser Met Pro Lys Ala Val Ile
820 825 830Gly Ser Ser Pro Asn Asp Asn Ile Asn Val Thr Glu Gln Gly Asp Asn
835 840 845Ile Ser Gly Val Asn Ser Lys Pro Leu Ser Asp Asp Val Arg Pro Asp
850 855 860Lys Lys Glu Leu Glu Asp Gln Asn Ser Asp Glu Ser Glu Glu Thr Val865 870 875 880Val Asn His Ile Ser Lys Ser Pro Ser Ile Asn Asn Gly Asp Asp Ser
885 890 895Gly Ser Gly Ser Ala Thr Val Ser Glu Ser Ser Ser Ser Asn Thr Gly
900 905 910Leu Ser Ile Asp Asp Asp Arg Asn Gly Asp Thr Phe Val Arg Thr Gln
915 920 925Asp Thr Ala Asn Thr Glu Asp Val Ile Arg Lys Glu Asn Ala Asp Lys
930 935 940Asp Glu Asp Glu Lys Gly Ala Asp Glu Glu Arg His Ser Thr Ser Glu945 950 955 960Ser Leu Ser Ser Pro Glu Glu Lys Met Leu Thr Asp Asn Glu Gly Gly
965 970 975Asn Ser Leu Asn His Glu Glu Val Lys Glu His Thr Ser Asn Ser Asp
980 985 990Asn Val Gln Gln Ser Gly Gly Ile Val Asn Met Asn Val Glu Lys Glu
995 1000 1005Leu Lys Asp Thr Leu Glu Asn Pro Ser Ser Ser Leu Asp Glu Gly Lys
1010 1015 1020Ala His Glu Glu Leu Ser Glu Pro Asn Leu Ser Ser Asp Gln Asp Met1025 1030 1035 1040Ser Asn Thr Pro Gly Pro Leu Asp Asn Thr Ser Glu Glu Thr Thr Glu
1045 1050 1055Arg Ile Ser Asn Asn Glu Tyr Lys Val Asn Glu Arg Glu Asp Glu Arg
1060 1065 1070Thr Leu Thr Lys Glu Tyr Glu Asp Ile Val Leu Lye Ser His Met Asn
1075 1080 1085Arg Glu Ser Asp Asp Gly Glu Leu Tyr Asp Glu Asn Ser Asp Leu Ser
1090 1095 1100Thr Val Asn Asp Glu Ser Glu Asp Ala Glu Ala Lys Met Lys Gly Asn1105 1110 1115 1120Asp Thr Ser Glu Met Ser His Asn Ser Ser Gln His Ile Glu Ser Asp
1125 1130 1135Gln Gln Lys Asn Asp Met Lys Thr Val Gly Asp Leu Gly Thr Thr His
1140 1145 1150Val Gln Asn Glu Ile Ser Val Pro Val Thr Gly Glu Ile Asp Glu Lys
1155 1160 1165Leu Arg Glu Ser Lys Glu Ser Lys Ile His Lys Ala Glu Glu Glu Arg
1170 1175 1180Leu Ser His Thr Asp Ile His Lys Ile Asn Pro Glu Asp Arg Asn Ser1185 1190 1195 1200Asn Thr Leu His Leu Lys Asp Ile Arg Asn Glu Glu Asn Glu Arg His
1205 1210 1215Leu Thr Asn Gln Asn Ile Asn Ile Ser Gln Glu Arg Asp Leu Gln Lys
1220 1225 1230Ala Val Asp Ser Met Glu Met Glu Phe Pro Lys Glu Val Lys Leu Ile
1235 1240 1245Ile Val Ile Met Glu Thr Asp Lys Ile Gly Gly Asn Ser Gly Asn Val
1250 1255 1260Leu Asn Met Arg Ser Asn Asn Asn Asn Phe Asn Asn Ile Pro Ser Arg1265 1270 1275 1280Tyr Asn Leu Tyr Asp Lys Lys Leu Asp Leu Asp Leu Tyr Glu Asn Arg
1285 1290 1295Asn Asp Ser Thr Thr Lys Glu Leu Ile Lys Lys Leu Ala Glu Ile Asn
1300 1305 1310Lys Cys Glu Asn Glu Ile Ser Val Lys Tyr Cys Asp His Met Ile His
1315 1320 1325Glu Glu Ile Pro Leu Lys Thr Cys Thr Lys Glu Lys Thr Arg Asn Leu
1330 1335 1340Cys Cys Ala Val Ser Asp Tyr Cys Met Ser Tyr Phe Thr Tyr Asp Ser1345 1350 1355 1360Glu Glu Tyr Tyr Asn Cys Thr Lys Arg Glu Phe Asp Asp Pro Ser Tyr
1365 1370 1375Thr Cys Phe Arg Lys Glu Ala Phe Ser Ser Met Ile Phe Lys Phe Leu
1380 1385 1390Ile Thr Asn Lys Ile Tyr Tyr Tyr Phe Tyr Thr Tyr Lys Thr Ala Lys
1395 1400 1405Val Thr Ile Lys Lys Ile Asn Phe Ser Leu Ile Phe Phe Phe Phe Phe
1410 1415 1420Ser Phe1425(2)SEQ ID NO:5资料:(I)序列特征:
(A)长度:2288个碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:DNA(基因组)(III)假定的:非(VI)原始来源:
(A)生物:镰状疟原虫(XI)序列描述:SEA ID NO:5:CACTTTATGC TTCCGGCTCG TATGTTGTGT GGAATTGTGA GCGGATAACA ATTTCACACA 60GGAAACAGCT ATGACCATGA TTACGCCAAG CTCTAATACG ACTCACTATA GGGAAAGCTG 120GTACGCCTGC AGGTCCGGTC CGGAATTCAA TAAAATATTT CCAGAAAGGA ATGTGCAAAT 180TCACATATCC AATATATTCA AGGAATATAA AGAAAATAAT GTAGATATCA TATTTGGAAC 240GTTGAATTAT GAATATAATA ATTTCTGTAA AGAAAAACCT GAATTAGTAT CTGCTGCCAA 300GTATAATCTG AAAGCTCCAA ATGCTAAATC CCCTAGAATA TACAAATCTA AGGAGCATGA 360AGAATCAAGT GTGTTTGGTT GCAAAACGAA AATCAGTAAA GTTAAAAAAA AATGGAATTG 420TTATAGTAAT AATAAAGTAA CTAAACCTGA AGGTGTATGT GGACCACCAA GAAGGCAACA 480ATTATGTCTT GGATATATAT TTTTGATTCG CGACGGTAAC GAGGAAGGAT TAAAAGATCA 540TATTAATAAG GCAGCTAATT ATGAGGCAAT GCATTTAAAA GAGAAATATG AGAATGCTGG 600TGGTGATAAA ATTTGCAATG CTATATTGGG AAGTTATGCA GATATTGGAG ATATTGTAAG 660AGGTTTGGAT GTTTGGAGGG ATATAAATAC TAATAAATTA TCAGAAAAAT TCCAAAAAAT 720TTTTATGGGT GGTGGTAATT CTAGGAAAAA ACAAAACGAT AATAATGAAC GTAATAAATG 780GTGGGAAAAA CAAAGGAATT TAATATGGTC TAGTATGGTA AAACACATTC CAAAAGGAAA 840AACATGTAAA CGTCATAATA ATTTTGAGAA AATTCCTCAA TTTTTGAGAT GGTTAAAAGA 900ATGGGGTGAT GAATTTTGTG AGGAAATGGG TACGGAAGTC AAGCAATTAG AGAAAATATG 960TGAAAATAAA AATTGTTCGG AAAAAAAATG TAAAAATGCA TGTAGTTCCT ATGAAAAATG 1020GATAAAGGAA CGAAAAAATG AATATAATTT GCAATCAAAG AAATTTGATA GTGATAAAAA 1080ATTAAATAAA AAAAACAATC TTTATAATAA ATTTGAGGAT TCTAAAGCTT ATTTAAGGAG 1140TGAATCAAAA CAGTGCTCAA ATATAGAATT TAATGATGAA ACATTTACAT TTCCTAATAA 1200ATATAAAGAG GCTTGTATGG TATGTGAAAA TCCTTCATCT TCGAAAGCTC TTAAACCTAT 1260AAAAACGAAT GTGTTTCCTA TAGAGGAATC AAAAAAATCT GAGTTATCAA GTTTAACAGA 1320TAAATCTAAG AATACTCCTA ATAGTTCTGG TGGGGGAAAT TATGGAGATA GACAAATATC 1380AAAAAGAGAC GATGTTCATC ATGATGGTCC TAAGGAAGTG AAATCCGGAG AAAAAGAGGT 1440ACCAAAAATA GATGCAGCTG TTAAAACAGA AAATGAATTT ACCTCTAATC GAAACGATAT 1500TGAAGGAAAG GAAAAAAGTA AAGGTGATCA TTCTTCTCCT GTTCATTCTA AAGATATAAA 1560AAATGAGGAA CCACAAAGGG TGGTGTCTGA AAATTTACCT AAAATTGAAG AGAAAATGGA 1620ATCTTCTGAT TCTATACCAA TTACTCATAT AGAAGCTGAA AAGGGTCAGT CTTCTAATTC 1680TAGCGATAAT GATCCTGCAG TAGTAAGTGG TAGAGAATCT AAAGATGTAA ATCTTCATAC 1740TTCTGAAAGG ATTAAAGAAA ATGAAGAAGG TGTGATTAAA ACAGATGATA GTTCAAAAAG 1800TATTGAAATT TCTAAAATAC CATCTGACCA AAATAATCAT AGTGATTTAT CACAGAATGC 1860AAATGAGGAC TCTAATCAAG GGAATAAGGA AACAATAAAT CCTCCTTCTA CAGAAAAAAA 1920TCTCAAAGAA ATTCATTATA AAACATCTGA TTCTGATGAT CATGGTTCTA AAATTAAAAG 1980TGAAATTGAA CCAAAGGAGT TAACGGAGGA ATCACCTCTT ACTGATAAAA AAACTGAAAG 2040TGCAGCGATT GGTGATAAAA ATCATGAATC AGTAAAAAGC GCTGATATTT TTCAATCTGA 2100GATTCATAAT TCTGATAATA GAGATAGAAT TGTTTCTGAA AGTGTAGTTC AGGATTCTTC 2160AGGAAGCTCT ATGAGTACTG AATCTATACG TACTGATAAC AAGGATTTTA AAACAAGTGA 2220GGATATTGCA CCTTCTATTA ATGGTCGGAA TTCCCGGGTC GACGAGCTCA CTAGTCGGCG 2280GCCGCTCT 2288(2)SEQ ID NO:6资料:(I)序列特征:
(A)长度:749个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:蛋白质(III)假定的:非(VI)原始来源:
(A)生物;镰状疟原虫(XI)序列描述:SEA ID NO:6:Ala Asp Asn Asn Phe Thr Gln Glu Thr Ala Met Thr Met Ile Thr Pro1 5 10 15Ser Ser Asn Thr Thr His Tyr Arg Glu Ser Trp Tyr Ala Cys Arg Ser
20 25 30Gly Pro Glu Phe Asn Lys Ile Phe Pro Glu Arg Asn Val Gln Ile His
35 40 45Ile Ser Asn Ile Phe Lys Glu Tyr LysGlu Asn Asn Val Asp Ile Ile
50 55 60Phe Gly Thr Leu Asn Tyr Glu Tyr Asn Asn Phe Cys Lys Glu Lys Pro65 70 75 80Glu Leu Val Ser Ala Ala Lys Tyr Asn Leu Lys Ala Pro Asn Ala Lys
85 90 95Ser Pro Arg Ile Tyr Lys Ser Lys Glu His Glu Glu Ser Ser Val Phe
100 105 110Gly Cys Lys Thr Lys Ile Ser Lys Val Lys Lys Lys Trp Asn Cys Tyr
115 120 125Ser Asn Asn Lys Val Thr Lys Pro Glu Gly Val Cys Gly Pro Pro Arg
130 135 140Arg Gln Gln Leu Cys Leu Gly Tyr Ile Phe Leu Ile Arg Asp Gly Asn145 150 155 160Glu Glu Gly Leu Lys Asp His Ile Asn Lys Ala Ala Asn Tyr Glu Ala
165 170 175Met His Leu Lys Glu Lys Tyr Glu Asn Ala Gly Gly Asp Lys Ile Cys
180 185 190Asn Ala Ile Leu Gly Ser Tyr Ala Asp Ile Gly Asp Ile Val Arg Gly
195 200 205Leu Asp Val Trp Arg Asp Ile Asn Thr Asn Lys Leu Ser Glu Lys Phe
210 215 220Gln Lys Ile Phe Met Gly Gly Gly Asn Ser Arg Lys Lys Gln Asn Asp225 230 235 240Asn Asn Glu Arg Asn Lys Trp Trp Glu Lys Gln Arg Asn Leu Ile Trp
245 250 255Ser Ser Met Val Lys His Ile Pro Lys Gly Lys Thr Cys Lys Arg His
260 265 270Asn Asn Phe Glu Lys Ile Pro Gln Phe Leu Arg Trp Leu Lys Glu Trp
275 280 285Gly Asp Glu Phe Cys Glu Glu Met Gly Thr Glu Val Lys Gln Leu Glu
290 295 300Lys Ile Cys Glu Asn Lys Asn Cys Ser Glu Lys Lys Cys Lys Asn Ala305 310 315 320Cys Ser Ser Tyr Glu Lys Trp Ile Lys Glu Arg Lys Asn Glu Tyr Asn
325 330 335Leu Gln Ser Lys Lys Phe Asp Ser Asp Lys Lys Leu Asn Lys Lys Asn
340 345 350Asn Leu Tyr Asn Lys Phe Glu Asp Ser Lys Ala Tyr Leu Arg Ser Glu
355 360 365Ser Lys Gln Cys Ser Asn Ile Glu Phe Asn Asp Glu Thr Phe Thr Phe
370 375 380Pro Asn Lys Tyr Lys Glu Ala Cys Met Val Cys Glu Asn Pro Ser Ser385 390 395 400Ser Lys Ala Leu Lys Pro Ile Lys Thr Asn Val Phe Pro Ile Glu Glu
405 410 415Ser Lys Lys Ser Glu Leu Ser Ser Leu Thr Asp Lys Ser Lys Asn Thr
420 425 430Pro Asn Ser Ser Gly Gly Gly Asn Tyr Gly Asp Arg Gln Ile Ser Lys
435 440 445Arg Asp Asp Val His His Asp Gly Pro Lys Glu Val Lys Ser Gly Glu
450 455 460Lys Glu Val Pro Lys Ile Asp Ala Ala Val Lys Thr Glu Asn Glu Phe465 470 475 480Thr Ser Asn Arg Asn Asp Ile Glu Gly Lys Glu Lys Ser Lys Gly Asp
485 490 495His Ser Ser Pro Val His Ser Lys Asp Ile Lys Asn Glu Glu Pro Gln
500 505 510Arg Val Val Ser Glu Asn Leu Pro Lys Ile Glu Glu Lys Met Glu Ser
515 520 525Ser Asp Ser Ile Pro Ile Thr His Ile Glu Ala Glu Lys Gly Gln Ser
530 535 540Ser Asn Ser Ser Asp Asn Asp Pro Ala Val Val Ser Gly Arg Glu Ser545 550 555 560Lys Asp Val Asn Leu His Thr Ser Glu Arg Ile Lys Glu Asn Glu Glu
565 570 575Gly Val Ile Lys Thr Asp Asp Ser Ser Lys Ser Ile Glu Ile Ser Lys
580 585 590Ile Pro Ser Asp Gln Asn Asn His Ser Asp Leu Ser Gln Asn Ala Asn
595 600 605Glu Asp Ser Asn Gln Gly Asn Lys Glu Thr Ile Asn Pro Pro Ser Thr
610 615 620Glu Lys Asn Leu Lys Glu Ile His Tyr Lys Thr Ser Asp Ser Asp Asp625 630 635 640His Gly Ser Lys Ile Lys Ser Glu Ile Glu Pro Lys Glu Leu Thr Glu
645 650 655Glu Ser Pro Leu Thr Asp Lys Lys Thr Glu Ser Ala Ala Ile Gly Asp
660 665 670Lys Asn His Glu Ser Val Lys Ser Ala Asp Ile Phe Gln Ser Glu Ile
675 680 685His Asn Ser Asp Asn Arg Asp Arg Ile VAl Ser Glu Ser Val Val Gln
690 695 700Asp Ser Ser Gly Ser Ser Met Ser Thr Glu Ser Ile Arg Thr Asp Asn705 710 715 720Lys Asp Phe Lys Thr Ser Glu Asp Ile Ala Pro Ser Ile Asn Gly Arg
725 730 735Asn Ser Arg Val Asp Glu Leu Thr Ser Arg Arg Pro Leu
740 745(2)SEQ ID NO:7资料:(I)序列特征:
(A)长度:2606个碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:DNA(基因组)(III)假定的:非(VI)原始来源:
(A)生物:镰状疟原虫(XI)序列描述:SEA ID NO:7:AGCTCTATTA CGACTCACTA TAGGGAAAGC TGGTACGCCT GCAGGTACCG GTCCGGAATT 60CCCGGGTCGA CGAGCTCACT AGTCGGCGGC CGCTCTAGAG GATCCAAGCT TAATAGTGTT 120TATACGTCTA TTGGCTTATT TTTAAATAGC TTAAAAAGCG GACCATGTAA AAAGGATAAT 180GATAATGCAG AGGATAATAT AGATTTTGGT GATGAAGGTA AAACATTTAA AGAGGCAGAT 240AATTGTAAAC CATGTTCTCA ATTTACTGTT GATTGTAAAA ATTGTAATGG TGGTGATACA 300AAAGGGAAGT GCAATGGCAG CAATGGCAAA AAGAATGGAA ATGATTATAT TACTGCAAGT 360GATATTGAAA ATGGAGGGAA TTCTATTGGA AATATAGATA TGGTTGTTAG TGATAAGGAT 420GCAAATGGAT TTAATGGTTT AGACGCTTGT GGAAGTGCAA ATATCTTTAA AGGTATTAGA 480AAAGAACAAT GGAAATGTGC TAAAGTATGT GGTTTAGATG TATGTGGTCT TAAAAATGGT 540AATGGTAGTA TAGATAAAGA TCAAAAACAA ATTATAATTA TTAGAGCATT GCTTAAACGT 600TGGGTAGAAT ATTTTTTAGA AGATTATAAT AAAATTAATG CCAAAATTTC ACATTGTACG 660AAAAAGGATA ATGAATCCAC ATGTACAAAT GATTGTCCAA ATAAATGTAC ATGTGTAGAA 720GAGTGGATAA ATCAGAAAAG GACAGAATGG AAAAATATAA AAAAACATTA CAAAACACAA 780AATGAAAATG GTGACAATAA CATGAAATCT TTGGTTACAG ATATTTTGGG TGCCTTGCAA 840CCCCAAAGTG ATGTTAACAA AGCTATAAAA CCTTGTAGTG GTTTAACTGC GTTCGAGAGT 900TTTTGTGGTC TTAATGGCGC TGATAACTCA GAAAAAAAAG AAGGTGAAGA TTACGATCTT 960GTTCTATGTA TGCTTAAAAA TCTTGAAAAA CAAATTCAGG AGTGCAAAAA GAAACATGGC 1020GAAACTAGTG TCGAAAATGG TGGCAAATCA TGTACCCCCC TTGACAACAC CACCCTTGAG 1080GAGGAACCCA TAGAAGAGGA AAACCAAGTG GAAGCGCCGA ACATTTGTCC AAAACAAACA 1140GTGGAAGATA AAAAAAAAGA GGAAGAAGAA GAAACTTGTA CACCGGCATC ACCAGTACCA 1200GAAAAACCGG TACCTCATGT GGCACGTTGG CGAACATTTA CACCACCTGA GGTATTCAAG 1260ATATGGAGGG GAAGGAGAAA TAAAACTACG TGCGAAATAG TGGCAGAAAT GCTTAAAGAT 1320AAGAATGGAA GGACTACAGT AGGTGAATGT TATAGAAAAG AAACTTATTC TGAATGGACG 1380TGTGATGAAA GTAAGATTAA AATGGGACAG CATGGAGCAT GTATTCCTCC AAGAAGACAA 1440AAATTATGTT TACATTATTT AGAAAAAATA ATGACAAATA CAAATGAATT GAAATACGCA 1500TTTATTAAAT GTGCTGCAGC AGAAACTTTT TTGTTATGGC AAAACTACAA AAAAGATAAG 1560AATGGTAATG CAGAAGATCT CGATGAAAAA TTAAAAGGTG GTATTATCCC CGAAGATTTT 1620AAACGGCAAA TGTTCTATAC GTTTGCAGAT TATAGAGATA TATGTTTGGG TACGGATATA 1680TCATCAAAAA AAGATACAAG TAAAGGTGTA GGTAAAGTAA AATGCAATAT TGATGATGTT 1740TTTTATAAAA TTAGCAATAG TATTCGTTAC CGTAAAAGTT GGTGGGAAAC AAATGGTCCA 1800GTTATATGGG AAGGAATGTT ATGCGCTTTA AGTTATGATA CGAGCCTAAA TAATGTTAAT 1860CCGGAAACTC ACAAAAAACT TACCGAAGGC AATAACAACT TTGAGAAAGT CATATTTGGT 1920AGTGATAGTA GCACTACTTT GTCCAAATTT TCTGAAAGAC CTCAATTTCT AAGATGGTTG 1980ACTGAATGGG GAGAAAATTT CTGCAAAGAA CAAAAAAAGG AGTATAAGGT GTTGTTGGCA 2040AAATGTAAGG ATTGTGATGT TGATGGTGAT GGTAAATGTA ATGGAAAATG TGTTGCGTGC 2100AAAGATCAAT GTAAACAATA TCATAGTTGG ATTGGAATAT GGATAGATAA TTATAAAAAA 2160CAAAAAGGAA GATATACTGA GGTTAAAAAA ATACCTCTGT ATAAAGAAGA TAAAGACGTG 2220AAAAACTCAG ATGATGCTCG CGATTATTTA AAAACACAAT TACAAAATAT GAAATGTGTA 2280AATGGAACTA CTGATGAAAA TTGTGAGTAT AAGTGTATGC ATAAAACCTC ATCCACAAAT 2340AGTGATATGC CCGAATCGTT GGACGAAAAG CCGGAAAAGG TCAAAGACAA GTGTAATTGT 2400GTACCTAATG AATGCAATGC ATTGAGTGTA AGTGGTAGCG GTTTTCCTGA TGGTCAAGCT 2460TACGTACGCG TGCATGCGAC GTCATAGCTC TTCTATAGTG TCACCTAAAT TCAATTCACT 2520GGCCGTCGTT TTACAACGTC GTGACTGGGA AAACCTGGCG TTACCCAACT TAATCGCCTT 2580GCAGCACATC CCCCTTTCGC CAGCTG 2606(2)SEQ ID NO:8资料:(I)序列特征:
(A)长度:921个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:蛋白质(III)假定的:非(VI)原始来源:
(A)生物:镰状疟原虫(XI)序列描述:SEA ID NO:8:Lys Leu Asn Ser Val Tyr Thr Ser Ile Gly Leu Phe Leu Asn Ser Leu1 5 10 15Lys Ser Gly Pro Cys Lys Lys Asp Asn Asp Asn Ala Glu Asp Asn Ile
20 25 30Asp Phe Gly Asp Glu Gly Lys Thr Phe Lys Glu Ala Asp Asn Cys Lys
35 40 45Pro Cys Ser Gln Phe Thr Val Asp Cys Lys Asn Cys Asn Gly Gly Asp
50 55 60Thr Lys Gly Lys Cys Asn Gly Ser Asn Gly Lys Lys Asn Gly Asn Asp65 70 75 80Tyr Ile Thr Ala Ser Asp Ile Glu Asn Gly Gly Asn Ser Ile Gly Asn
85 90 95Ile Asp Met Val Val Ser Asp Lys Asp Ala Asn Gly Phe Asn Gly Leu
100 105 110Asp Ala Cys Gly Ser Ala Asn Ile Phe Lys Gly Ile Arg Lys Glu GLn
115 120 125Trp Lys Cys Ala Lys Val Cys Gly Leu Asp Val Cys Gly Leu Lys Asn
130 135 140Gly Asn Gly Ser Ile Asp Lys Asp Gln Lys Gln Ile Ile Ile Ile Arg145 150 155 160Ala Leu Leu Lys Arg Trp Val Glu Tyr Phe Leu Glu Asp Tyr Asn Lys
165 170 175Ile Asn Ala Lys Ile Ser His Cys Thr Lys Lys Asp Asn Glu Ser Thr
180 185 190Cys Thr Asn Asp Cys Pro Asn Lys Cys Thr Cys Val Glu Glu Trp Ile
195 200 205Asn Gln Lys Arg Thr Glu Trp Lys Asn Ile Lys Lys His Tyr Lys Thr
210 215 220Gln Asn Glu Asn Gly Asp Asn Asn Met Lys Ser Leu Val Thr Asp Ile225 230 235 240Leu Gly Ala Leu Gln Pro Gln Ser Asp Val Asn Lys Ala Ile Lys Pro
245 250 255Cys Ser Gly Leu Thr Ala Phe Glu Ser Phe Cys Gly Leu Asn Gly Ala
260 265 270Asp Asn Ser Glu Lys Lys Glu Gly Glu Asp Tyr Asp Leu Val Leu Cys
275 280 285Met Leu Lys Asn Leu Glu Lys Gln Ile Gln Glu Cys Lys Lys Lys His
290 295 300Gly Glu Thr Ser Val Glu Asn Gly Gly Lys Ser Cys Thr Pro Leu Asp305 310 315 320Asn Thr Thr Leu Glu Glu Glu Pro Ile Glu Glu Glu Asn Gln Val Glu
325 330 335Ala Pro Asn Ile Cys Pro Lys Gln Thr Val Glu Asp Lys Lys Lys Glu
340 345 350Glu Glu Glu Glu Thr Cys Thr Pro Ala Ser Pro Val Pro Glu Lys Pro
355 360 365Val Pro His Val Ala Arg Trp Arg Thr Phe Thr Pro Pro Glu Val Phe
370 375 380Lys Ile Trp Arg Gly Arg Arg Asn Lys Thr Thr Cys Glu Ile Val Ala385 390 395 400Glu Met Leu Lys Asp Lys Asn Gly Arg Thr Thr Val Gly Glu Cys Tyr
405 410 415Arg Lys Glu Thr Tyr Ser Glu Trp Thr Cys Asp Glu Ser Lys Ile Lys
420 425 430Met Gly Gln His Gly Ala Cys Ile Pro Pro Arg Arg Gln Lys Leu Cys
435 440 445Leu His Tyr Leu Glu Lys Ile Met Thr Asn Thr Asn Glu Leu Lys Tyr
450 455 460Ala Phe Ile Lys Cys Ala Ala Ala Glu Thr Phe Leu Leu Trp Gln Asn465 470 475 480Tyr Lys Lys Asp Lys Asn Gly Asn Ala Glu Asp Leu Asp Glu Lys Leu
485 490 495Lys Gly Gly Ile Ile Pro Glu Asp Phe Lys Arg Gln Met Phe Tyr Thr
500 505 510Phe Ala Asp Tyr Arg Asp Ile Cys Leu Gly Thr Asp Ile Ser Ser Lys
515 520 525Lys Asp Thr Ser Lys Gly Val Gly Lys Val Lys Cys Asn Ile Asp Asp
530 535 540Val Phe Tyr Lys Ile Ser Asn Ser Ile Arg Tyr Arg Lys Ser Trp Trp545 550 555 560Glu Thr Asn Gly Pro Val Ile Trp Glu Gly Met Leu Cys Ala Leu Ser
565 570 575Tyr Asp Thr Ser Leu Asn Asn Val Asn Pro Glu Thr His Lys Lys Leu
580 585 590Thr Glu Gly Asn Asn Asn Phe Glu Lys Val Ile Phe Gly Ser Asp Ser
595 600 605Ser Thr Thr Leu Ser Lys Phe Ser Glu Arg Pro Gln Phe Leu Arg Trp
610 615 620Leu Thr Glu Trp Gly Glu Asn Phe Cys Lys Glu Gln Lys Lys Glu Tyr625 630 635 640Lys Val Leu Leu Ala Lys Cys Lys Asp Cys Asp Val Asp Gly Asp Gly
645 650 655Lys Cys Asn Gly Lys Cys Val Ala Cys Lys Asp Gln Cys Lys Gln Tyr
660 665 670His Ser Trp Ile Gly Ile Trp Ile Asp Asn Tyr Lys Lys Gln Lys Gly
675 680 685Arg Tyr Thr Glu Val Lys Lys Ile Pro Leu Tyr Lys Glu Asp Lys Asp
690 695 700Val Lys Asn Ser Asp Asp Ala Arg Asp Tyr Leu Lys Thr Gln Leu Gln705 710 715 720Asn Met Lys Cys Val Asn Gly Thr Thr Asp Glu Asn Cys Glu Tyr Lys
725 730 735Cys Met His Lys Thr Ser Ser Thr Asn Ser Asp Met Pro Glu Ser Leu
740 745 750Asp Glu Lys Pro Glu Lys Val Lys Asp Lys Cys Asn Cys Val Pro Asn
755 760 765Glu Cys Asn Ala Leu Ser Val Ser Gly Ser Gly Phe Pro Asp Gly Gln
770 775 780Ala Phe Gly Gly Gly Val Leu Glu Gly Thr Cys Lys Gly Leu Gly Glu785 790 795 800Pro Lys Lys Lys Ile Glu Pro Pro Gln Tyr Asp Pro Thr Asn Asp Ile
805 810 815Leu Lys Ser Thr Ile Pro Val Thr Ile Val Leu Ala Leu Gly Ser Ile
820 825 830Ala Phe Leu Phe Met Lys Val Ile Tyr Ile Tyr Val Trp Tyr Ile Tyr
835 840 845Met Leu Cys Val Gly Ala Leu Asp Thr Tyr Ile Cys Gly Cys Ile Cys
850 855 860Ile Cys Ile Phe Ile Cys Val Ser Val Tyr Val Cys Val Tyr Val Tyr865 870 875 880Val Phe Leu Tyr Met Cys Val Phe Tyr Ile Tyr Phe Ile Tyr Ile Tyr
885 890 895Val Phe Ile Leu Lys Met Lys Lys Met Lys Lys Met Lys Lys Met Lys
900 905 9l0Lys Met Lys Lys Arg Lys Lys Arg Ile
915 920(2)SEQ ID NO:9资料:(I)序列特征:
(A)长度:2101碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:DNA(基因组)(III)假定的:非(VI)原始来源:
(A)生物:镰状疟原虫
(XI)序列描述:SEA ID NO:9:GGAACAGGGT GATAATAAAG TAGGAGCCTG TGCTCCGTAT AGACGATTAC ATTTATGTGA 60TTATAATTTG GAATCTATAG ACACAACGTC GACGACGCAT AAGTTGTTGT TAGAGGTGTG 120TATGGCAGCA AAATACGAAG GAAACTCAAT AAATACACAT TATACACAAC ATCAACGAAC 180TAATGAGGAT TCTGCTTCCC AATTATGTAC TGTATTAGCA CGAAGTTTTG CAGATATAGG 240TGATATCGTA AGAGGAAAAG ATCTATATCT CGGTTATGAT AATAAAGAAA AAGAACAAAG 300AAAAAAATTA GAACAGAAAT TGAAAGATAT TTTCAAGAAA ATACATAAGG ACGTGATGAA 360GACGAATGGC GCACAAGAAC GCTACATAGA TGATGCCAAA GGAGGAGATT TTTTTCAATT 420AAGAGAAGAT TGGTGGACGT CGAATCGAGA AACAGTATGG AAAGCATTAA TATGTCATGC 480ACCAAAAGAA GCTAATTATT TTATAAAAAC AGCGTGTAAT GTAGGAAAAG GAACTAATGG 540TCAATGCCAT TGCATTGGTG GAGATGTTCC CACATATTTC GATTATGTGC CGCAGTATCT 600TCGCTGGTTC GAGGAATGGG CAGAAGACTT TTGCAGGAAA AAAAAAAAAA AACTAGAAAA 660TTTGCAAAAA CAGTGTCGTG ATTACGAACA AAATTTATAT TGTAGTGGTA ATGGCTACGA 720TTGCACAAAA ACTATATATA AAAAAGGTAA ACTTGTTATA GGTGAACATT GTACAAACTG 780TTCTGTTTGG TGTCGTATGT ATGAAACTTG GATAGATAAC CAGAAAAAAG AATTTCTAAA 840ACAAAAAAGA AAATACGAAA CAGAAATATC AGGTGGTGGT AGTGGTAAGA GTCCTAAAAG 900GACAAAACGG GCTGCACGTA GTAGTAGTAG TAGTGATGAT AATGGGTATG AAAGTAAATT 960TTATAAAAAA CTGAAAGAAG TTGGCTACCA AGATGTCGAT AAATTTTTAA AAATATTAAA 1020CAAAGAAGGA ATATGTCAAA AACAACCTCA AGTAGGAAAT GAAAAAGCAG ATAATGTTGA 1080TTTTACTAAT GAAAAATATG TAAAAACATT TTCTCGTACA GAAATTTGTG AACCGTGCCC 1140ATGGTGTGGA TTGGAAAAAG GTGGTCCACC ATGGAAAGTT AAAGGTGACA AAACCTGCGG 1200AAGTGCAAAA ACAAAGACAT ACGATCCTAA AAATATTACC GATATACCAG TACTCTACCC 1260TGATAAATCA CAGCAAAATA TACTAAAAAA ATATAAAAAT TTTTGTGAAA AAGGTGCACC 1320TGGTGGTGGT CAAATTAAAA AATGGCAATG TTATTATGAT GAACATAGGC CTAGTAGTAA 1380AAATAATAAT AATTGTGTAG AAGGAACATG GGACAAGTTT ACACAAGGTA AACAAACCGT 1440TAAGTCCTAT AATGTTTTTT TTTGGGATTG GGTTCATGAT ATGTTACACG ATTCTGTAGA 1500GTGGAAGACA GAACTTAGTA AGTGTATAAA TAATAACACT AATGGCAACA CATGTAGAAA 1560CAATAATAAA TGTAAAACAG ATTGTGGTTG TTTTCAAAAA TGGGTTGAAA AAAAACAACA 1620AGAATGGATG GCAATAAAAG ACCATTTTGG AAAGCAAACA GATATTGTCC AACAAAAAGG 1680TCTTATCGTA TTTAGTCCCT ATGGAGTTCT TGACCTTGTT TTGAAGGGCG GTAATCTGTT 1740GCAAAATATT AAAGATGTTC ATGGAGATAC AGATGACATA AAACACATTA AGAAACTGTT 1800GGATGAGGAA GACGCAGTAG CAGTTGTTCT TGGTGGCAAG GACAATACCA CAATTGATAA 1860ATTACTACAA CACGAAAAAG AACAAGCAGA ACAATGCAAA CAAAAGCAGG AAGAATGCGA 1920GAAAAAAGCA CAACAAGAAA GTCGTGGTCG CTCCGCCGAA ACCCGCGAAG ACGAAAGGAC 1980ACAACAACCT GCTGATAGTG CCGGCGAAGT CGAAGAAGAA GAAGACGACG ACGACTACGA 2040CGAAGACGAC GAAGATGACG ACGTAGTCCA GGACGTAGAT GTAAGTGAAA TAAGAGGTCC 2100G 2101(2)SEQ ID NO:10资料:(I)序列特征:
(A)长度:700个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:蛋白质(III)假定的:无(VI)原始来源:
(A)生物:镰状疟原虫(XI)序列描述:SEA ID NO:10:Glu Gln Gly Asp Asn Lys Val Gly Ala Cys Ala Pro Tyr Arg Arg Leu1 5 10 15His Leu Cys Asp Tyr Asn Leu Glu Ser Ile Asp Thr Thr Ser Thr Thr
20 25 30His Lys Leu Leu Leu Glu Val Cys Met Ala Ala Lys Tyr Glu Gly Asn
35 40 45Ser Ile Asn Thr His Tyr Thr Gln His Gln Arg Thr Asn Glu Asp Ser
50 55 60Ala Ser Gln Leu Cys Thr Val Leu Ala Arg Ser Phe Ala Asp Ile Gly65 70 75 80Asp Ile Val Arg Gly Lys Asp Leu Tyr Leu Gly Tyr Asp Asn Lys Glu
85 90 95Lys Glu Gln Arg Lys Lys Leu Glu Gln Lys Leu Lys Asp Ile Phe Lys
100 105 110Lys Ile His Lys Asp Val Met Lys Thr Asn Gly Ala Gln Glu Arg Tyr
115 120 125Ile Asp Asp Ala Lys Gly Gly Asp Phe Phe Gln Leu Arg Glu Asp Trp
130 135 140Trp Thr Ser Asn Arg Glu Thr Val Trp Lys Ala Leu Ile Cys His Ala145 150 155 160Pro Lys Glu Ala Asn Tyr Phe Ile Lys Thr Ala Cys Asn Val Gly Lys
165 170 175Gly Thr Asn Gly Gln Cys His Cys Ile Gly Gly Asp Val Pro Thr Tyr
180 185 190Phe Asp Tyr Val Pro Gln Tyr Leu Arg Trp Phe Glu Glu Trp Ala Glu
195 200 205Asp Phe Cys Arg Lys Lys Lys Lys Lys Leu Glu Asn Leu Gln Lys Gln
210 215 220Cys Arg Asp Tyr Glu Gln Asn Leu Tyr Cys Ser Gly Asn Gly Tyr Asp225 230 235 240Cys Thr Lys Thr Ile Tyr Lys Lys Gly Lys Leu Val Ile Gly Glu His
245 250 255Cys Thr Asn Cys Ser Val Trp Cys Arg Met Tyr Glu Thr Trp Ile Asp
260 265 270Asn Gln Lys Lys Glu Phe Leu Lys Gln Lys Arg Lys Tyr Glu Thr Glu
275 280 285Ile Ser Gly Gly Gly Ser Gly Lys Ser Pro Lys Arg Thr Lys Arg Ala
290 295 300Ala Arg Ser Ser Ser Ser Ser Asp Asp Asn Gly Tyr Glu Ser Lys Phe305 310 315 320Tyr Lys Lys Leu Lys Glu Val Gly Tyr Gln Asp Val Asp Lys Phe Leu
325 330 335Lys Ile Leu Asn Lys Glu Gly Ile Cys Gln Lys Gln Pro Gln Val Gly
340 345 350Asn Glu Lys Ala Asp Asn Val Asp Phe Thr Asn Glu Lys Tyr Val Lys
355 360 365Thr Phe Ser Arg Thr Glu Ile Cys Glu Pro Cys Pro Trp Cys Gly Leu
370 375 380Glu Lys Gly Gly Pro Pro Trp Lys Val Lys Gly Asp Lys Thr Cys Gly385 390 395 400Ser Ala Lys Thr Lys Thr Tyr Asp Pro Lys Asn Ile Thr Asp Ile Pro
405 410 415Val Leu Tyr Pro Asp Lys Ser Gln Gln Asn Ile Leu Lys Lys Tyr Lys
420 425 430Asn Phe Cys Glu Lys Gly Ala Pro Gly Gly Gly Gln Ile Lys Lys Trp
435 440 445Gln Cys Tyr Tyr Asp Glu His Arg Pro Ser Ser Lys Asn Asn Asn Asn
450 455 460Cys Val Glu Gly Thr Trp Asp Lys Phe Thr Gln Gly Lys Gln Thr Val465 470 475 480Lys Ser Tyr Asn Val Phe Phe Trp Asp Trp Val His Asp Met Leu His
485 490 495Asp Ser Val Glu Trp Lys Thr Glu Leu Ser Lys Cys Ile Asn Asn Asn
500 505 510Thr Asn Gly Asn Thr Cys Arg Asn Asn Asn Lys Cys Lys Thr Asp Cys
515 520 525Gly Cys Phe Gln Lys Trp Val Glu Lys Lys Gln Gln Glu Trp Met Ala
530 535 540Ile Lys Asp His Phe Gly Lys Gln Thr Asp Ile Val Gln Gln Lys Gly545 550 555 560Leu Ile Val Phe Ser Pro Tyr Gly Val Leu Asp Leu Val Leu Lys Gly
565 570 575Gly Asn Leu Leu Gln Asn Ile Lys Asp Val His Gly Asp Thr Asp Asp
580 585 590Ile Lys His Ile Lys Lys Leu Leu Asp Glu Glu Asp Ala Val Ala Val
595 600 605Val Leu Gly Gly Lys Asp Asn Thr Thr Ile Asp Lys Leu Leu Gln His
610 615 620Glu Lys Glu Gln Ala Glu Gln Cys Lys Gln Lys Gln Glu Glu Cys Glu625 630 635 640Lys Lys Ala Gln Gln Glu Ser Arg Gly Arg Ser Ala Glu Thr Arg Glu
645 650 655Asp Glu Arg Thr Gln Gln Pro Ala Asp Ser Ala Gly Glu Val Glu Glu
660 665 670Glu Glu Asp Asp Asp Asp Tyr Asp Glu Asp Asp Glu Asp Asp Asp Val
675 680 685Val Gln Asp Val Asp Val Ser Glu Ile Arg Gly Pro
690 695 700(2)SEQ ID NO:11资料:(I)序列特征:
(A)长度:8220个碱基对
(B)类型:核酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:DNA(基因组)(III)假定的:非(VI)原姑来源:
(A)生物:镰状疟原虫(XI)序列描述:SEA ID NO:11:AAAAATGGGG CCCAAGGAGG CTGCAGGTGG GGATGATATT GAGGATGAAA GTGCCAAACA 60TATGTTTGAT AGGATAGGAA AAGATGTGTA CGATAAAGTA AAAGAGGAAG CTAAAGAACG 120TGGTAAAGGC TTGCAAGGAC GTTTGTCAGA AGCAAAATTT GAGAAAAATG AAAGCGATCC 180ACAAACACCA GAAGATCCAT GCGATCTTGA TCATAAATAT CATACAAATG TAACTACTAA 240TGTAATTAAT CCGTGCGCTG ATAGATCTGA CGTGCGTTTT TCCGATGAAT ATGGAGGTCA 300ATGTACACAT AATAGAATAA AAGATAGTCA ACAGGGTGAT AATAAAGGTG CATGTGCTCC 360ATATAGGCGA TTGCATGTAT GCGATCAAAA TTTAGAACAG ATAGAGCCTA TAAAAATAAC 420AAATACTCAT AATTTATTGG TAGATGTGTG TATGGCAGCA AAATTTGAAG GACAATCAAT 480AACACAAGAT TATCCAAAAT ATCAAGCAAC ATATGGTGAT TCTCCTTCTC AAATATGTAC 540TATGCTGGCA CGAAGTTTTG CGGACATAGG GGACATTGTC AGAGGAAGAG ATTTGTATTT 600AGGTAATCCA CAAGAAATAA AACAAAGACA ACAATTAGAA AATAATTTGA AAACAATTTT 660CGGGAAAATA TATGAAAAAT TGAATGGCGC AGAAGCACGC TACGGAAATG ATCCGGAATT 720TTTTAAATTA CGAGAAGATT GGTGGACTGC TAATCGAGAA ACAGTATGGA AAGCCATCAC 780ATGTAACGCT TGGGGTAATA CATATTTTCA TGCAACGTGC AATAGAGGAG AACGAACTAA 840AGGTTACTGC CGGTGTAACG ACGACCAAGT TCCCACATAT TTTGATTATG TGCCGCAGTA 900TCTTCGCTGG TTCGAGGAAT GGGCAGAAGA TTTTTGTAGG AAAAAAAATA AAAAAATAAA 960AGATGTTAAA AGAAATTGTC GTGGAAAAGA TAAAGAGGAT AAGGATCGAT ATTGTAGCCG 1020TAATGGCTAC GATTGCGAAA AAACTAAACG AGCGATTGGT AAGTTGCGTT ATGGTAAGCA 1080ATGCATTAGC TGTTTGTATG CATGTAATCC TTACGTTGAT TGGATAAATA ACCAAAAAGA 1140ACAATTTGAC AAACAGAAAA AAAAATATGA TGAAGAAATA AAAAAATATG AAAATGGAGC 1200ATCAGGTGGT AGTAGGCAAA AACGGGATGC AGGTGGTACA ACTACTACTA ATTATGATGG 1260ATATGAAAAA AAATTTTATG ACGAACTTAA TAAAAGTGAA TATAGAACCG TTGATAAATT 1320TTTGGAAAAA TTAAGTAATG AAGAAATATG CACAAAAGTT AAAGACGAAG AAGGAGGAAC 1380AATTGATTTT AAAAACGTTA ATAGTGATAG TACTAGTGGT GCTAGTGGCA CTAATGTTGA 1440AAGTCAAGGA ACATTTTATC GTTCAAAATA TTGCCAACCC TGCCCTTATT GTGGAGTGAA 1500AAAGGTAAAT AATGGTGGTA GTAGTAATGA ATGGGAAGAG AAAAATAATG GCAAGTGCAA 1560GAGTGGAAAA CTTTATGAGC CTAAACCCGA CAAAGAAGGT ACTACTATTA CAATCCTTAA 1620AAGTGGTAAA GGACATGATG ATATTGAAGA AAAATTAAAC AAATTTTGTG ATGAAAAAAA 1680TGGTGATACA ATAAATAGTG GTGGTAGTGG TACGGGTGGT AGTGGTGGTG GTAACAGTGG 1740TAGACAGGAA TTGTATGAAG AATGGAAATG TTATAAAGGT GAAGATGTAG TGAAAGTTGG 1800ACAGGATGAG GATGACGAGG AGGATTATGA AAATGTAAAA AATGCAGGCG GATTATGTAT 1860ATTAAAAAAC CAAAAAAAGA ATAAAGAAGA AGGTGGAAAT ACGTCTGAAA AGGAGCCTGA 1920TGAAATCCAA AAGACATTCA ATCCTTTTTT TTACTATTGG GTTGCACATA TGTTAAAAGA 1980TTCCATACAT TGGAAAAAAA AACTTCAGAG ATGTTTACAA AATGGTAACA GAATAAAATG 2040TGGAAACAAT AAATGTAATA ATGATTGTGA ATGTTTTAAA AGATGGATTA CACAAAAAAA 2100AGACGAATGG GGGAAAATAG TACAACATTT TAAAACGCAA AATATTAAAG GTAGAGGAGG 2160TAGTGACAAT ACGGCAGAAT TAATCCCATT TGATCACGAT TATGTTCTTC AATACAATTT 2220GCAAGAAGAA TTTTTGAAAG GCGATTCCGA AGACGCTTCC GAAGAAAAAT CCGAAAATAG 2280TCTGGATGCA GAGGAGGCAG AGGAACTAAA ACACCTTCGC GAAATCATTG AAAGTGAAGA 2340CAATAATCAA GAAGCATCTG TTGGTGGTGG CGTCACTGAA CAAAAAAATA TAATGGATAA 2400ATTGCTCAAC TACGAAAAAG ACGAAGCCGA TTTATGCCTA GAAATTCACG AAGATGAGGA 2460AGAGGAAAAA GAAAAAGGAG ACGGAAACGA ATGTATCGAA GAGGGCGAAA ATTTTCGTTA 2520TAATCCATGT AGTGGCGAAA GTGGTAACAA ACGATACCCC GTTCTTGCGA ACAAAGTAGC 2580GTATCAAATG CATCACAAGG CAAAGACACA ATTGGCTAGT CGTGCTGGTA GAAGTGCGTT 2640GAGAGGTGAT ATATCCTTAG CGCAATTTAA AAATGGTCGT AACGGAAGTA CATTGAAAGG 2700ACAAATTTGC AAAATTAACG AAAACTATTC CAATGATAGT CGTGGTAATA GTGGTGGACC 2760ATGTACAGGC AAAGATGGAG ATCACGGAGG TGTGCGCATG AGAATAGGAA CGGAATGGTC 2820AAATATTGAA GGAAAAAAAC AAACGTCATA CAAAAACGTC TTTTTACCTC CCCGACGAGA 2880ACACATGTGT ACATCCAATT TAGAAAATTT AGATGTTGGT AGTGTCACTA AAAATGATAA 2940GGCTAGCCAC TCATTATTGG GAGATGTTCA GCTCGCAGCA AAAACTGATG CAGCTGAGAT 3000AATAAAACGC TATAAAGATC AAAATAATAT ACAACTAACT GATCCAATAC AACAAAAAGA 3060CCAGGAGGCT ATGTGTCGAG CTGTACGTTA TAGTTTTGCC GATTTAGGAG ACATTATTCG 3120AGGAAGAGAT ATGTGGGATG AGGATAAGAG CTCAACAGAC ATGGAAACAC GTTTGATAAC 3180CGTATTTAAA AACATTAAAG AAAAACATGA TGGAATCAAA GACAACCCTA AATATACCGG 3240TGATGAAAGC AAAAAGCCCG CATATAAAAA ATTACGAGCA GATTGGTGGG AAGCAAATAG 3300ACATCAAGTG TGGAGAGCCA TGAAATGCGC AACAAAAGGC ATCATATGTC CTGGTATGCC 3360AGTTGACGAT TATATCCCCC AACGTTTACG CTGGATGACT GAATGGGCTG AATGGTATTG 3420TAAAGCGCAA TCACAGGAGT ATGACAAGTT AAAAAAAATC TGTGCAGATT GTATGAGTAA 3480GGGTGATGGA AAATGTACGC AAGGTGATGT CGATTGTGGA AAGTGCAAAG CAGCATGTGA 3540TAAATATAAA GAGGAAATAG AAAAATGGAA TGAACAATGG AGAAAAATAT CAGATAAATA 3600CAATCTATTA TACCTACAAG CAAAAACTAC TTCTACTAAT CCTGGCCGTA CTGTTCTTGG 3660TGATGACGAT CCCGACTATC AACAAATGGT AGATTTTTTG ACCCCAATAC ACAAAGCAAG 3720TATTGCCGCA CGTGTTCTTG TTAAACGTGC TGCTGGTAGT CCCACTGAGA TCGCCGCCGC 3780CGCCCCGATC ACCCCCTACA GTACTGCTGC CGGATATATA CACCAGGAAA TAGGATATGG 3840GGGGTGCCAG GAACAAACAC AATTTTGTGA AAAAAAACAT GGTGCAACAT CAACTAGTAC 3900CACGAAAGAA AACAAAGAAT ACACCTTTAA ACAACCTCCG CCGGAGTATG CTACAGCGTG 3960TGATTGCATA AATAGGTCGC AAACAGAGGA GCCGAAGAAA AAGGAAGAAA ATGTAGAGAG 4020TGCCTGCAAA ATAGTGGAGA AAATACTTGA GGGTAAGAAT GGAAGGACTA CAGTAGGTGA 4080ATGTAATCCA AAAGAGAGTT ATCCTGATTG GGATTGCAAA AACAATATTG ACATTAGTCA 4140TGATGGTGCT TGTATGCCTC CAAGGAGACA AAAACTATGT TTATATTATA TAGCACATGA 4200GAGTCAAACA GAAAATATAA AAACAGACGA TAATTTGAAA GATGCTTTTA TTAAAACTGC 4260AGCAGCAGAA ACTTTTCTTT CATGGCAATA TTATAAGAGT AAGAATGATA GTGAAGCTAA 4320AATATTAGAT AGAGGCCTTA TTCCATCCCA ATTTTTAAGA TCCATGATGT ACACGTTTGG 4380AGATTATAGA GATATATGTT TGAACACAGA TATATCTAAA AAACAAAATG ATGTAGCTAA 4440GGCAAAAGAT AAAATAGGTA AATTTTTCTC AAAAGATGGC AGCAAATCTC GTAGTGGCTT 4500ATCACGCCAA GAATGGTGGA AAACAAATGG TCCAGAGATT TGGAAAGGAA TGTTATGTGC 4560CTTAACAAAA TACGTCACAG ATACCGATAA CAAAAGAAAA ATCAAAAACG ACTACTCATA 4620CGATAAAGTC AACCAATCCC AAAATGGCAA CCCTTCCCTT GAAGAGTTTG CTGCTAAACC 4680TCAATTTCTA CGTTGGATGA TCGAATGGGG AGAAGAGTTT TGTGCTGAAC GTCAGAAGAA 4740GGAAAATATC ATAAAAGATG CATGTAATGA AATAAATTCT ACACAACAGT GTAATGATGC 4800GAAACATCGT TGTAATCAAG CATGTAGAGC ATATCAAGAA TATGTTGAAA ATAAAAAAAA 4860AGAATTTTCG GGACAAACAA ATAACTTTGT TCTAAAGGCA AATGTTCAGC CCCAAGATCC 4920AGAATATAAA GGATATGAAT ATAAAGACGG CGTACAACCG ATACAGGGGA ATGAGTATTT 4980ACTGCAAAAA TGTGATAATA ATAAATGTTC TTGCATGGAT GGAAATGTAC TTTCCGTCTC 5040TCCAAAAGAA AAACCTTTTG GAAAATATGC CCATAAATAT CCTGAGAAAT GTGATTGTTA 5100TCAAGGAAAA CATGTACCTA GCATACCACC TCCCCCCCCA CCTGTACAAC CACAACCGGA 5160AGCACCAACA GTAACAGTAG ACGTTTGCAG CATAGTAAAA ACACTATTTA AAGACACAAA 5220CAATTTTTCC GACGCTTGTG GTCTAAAATA CGGCAAAACC GCACCATCCA GTTGGAAATG 5280TATACCAAGT GACACAAAAA GTGGTGCTGG TGCCACCACC GGCAAAAGTG GTAGTGATAG 5340TGGTAGTATT TGTATCCCAC CCAGGAGGCG ACGATTATAT GTGGGGAAAC TACAGGAGTG 5400GGCTACCGCG CTCCCACAAG GTGAGGGCGC CGCGCCGTCC CACTCACGCG CCGACGACTT 5460GCGCAATGCG TTCATCCAAT CTGCTGCAAT AGAGACTTTT TTCTTATGGG ATAGATATAA 5520AGAAGAGAAA AAACCACAGG GTGATGGGTC ACAACAAGCA CTATCACAAC TAACCAGTAC 5580ATACAGTGAT GACGAGGAGG ACCCCCCCGA CAAACTGTTA CAAAATGGTA AGATACCCCC 5640CGATTTTTTG AGATTAATGT TCTATACATT AGGAGATTAT AGGGATATTT TAGTACACGG 5700TGGTAACACA AGTGACAGTG GTAACACAAA TGGTAGTAAC AACAACAATA TTGTGCTTGA 5760AGCGAGTGGT AACAAGGAGG ACATGCAAAA AATACAAGAG AAAATAGAAC AAATTCTCCC 5820AAAAAATGGT GGCACACCTC TTGTCCCAAA ATCTAGTGCC CAAACACCTG ATAAATGGTG 5880GAATGAACAC GCCGAATCTA TCTGGAAAGG TATGATATGT GCATTGACAT ATACAGAAAA 5940GAACCCTGAC ACCAGTGCAA GAGGCGACGA AAACAAAATA GAAAAGGATG ATGAAGTGTA 6000CGAGAAATTT TTTGGCAGCA CAGCCGACAA ACATGGCACA GCCTCAACCC CAACCGGCAC 6060ATACAAAACC CAATACGACT ACGAAAAAGT CAAACTTGAG GATACAAGTG GTGCCAAAAC 6120CCCCTCAGCC TCTAGTGATA CACCCCTTCT CTCCGATTTC GTGTTACGCC CCCCCTACTT 6180CCGTTACCTT GAAGAATGGG GTCAAAATTT TTGTAAAAAA AGAAAGCATA AATTGGCACA 6240AATAAAACAT GAGTGTAAAG TAGAAGAAAA TGGTGGTGGT AGTCGTCGTG GTGGTATAAC 6300AAGACAATAT AGTGGGGATG GCGAAGCGTG TAATGAGATG CTTCCAAAAA ACGATGGAAC 6360TGTTCCGGAT TTAGAAAAGC CGAGTTGTGC CAAACCTTGT AGTTCTTATA GAAAATGGAT 6420AGAAAGCAAG GGAAAAGAGT TTGAGAAACA AGAAAAGGCA TATGAACAAC AAAAAGACAA 6480ATGTGTAAAT GGAAGTAATA AGCATGATAA TGGATTTTGT GAAACACTAA CAACGTCCTC 6540TAAAGCTAAA GACTTTTTAA AAACGTTAGG ACCATGTAAA CCTAATAATG TAGAGGGTAA 6600AACAATTTTT GATGATGATA AAACCTTTAA ACATACAAAA GATTGTGATC CATGTCTTAA 6660ATTTAGTGTT AATTGTAAAA AAGATGAATG TGATAATTCT AAAGGAACCG ATTGCCGAAA 6720TAAAAATAGT ATTGATGCAA CAGATATTGA AAATGGAGTG GATTCTACTG TACTAGAAAT 6780GCGTGTCAGT GCTGATAGTA AAAGTGGATT TAATGGTGAT GGTTTAGAGA ATGCTTGTAG 6840AGGTGCTGGT ATCTTTGAAG GTATTAGAAA AGATGAATGG AAATGTCGTA ATGTATGTGG 6900TTATGTTGTA TGTAAACCGG AAAACGTTAA TGGGGAAGCA AAGGGAAAAC ACATTATACA 6960AATTAGAGCA CTGGTTAAAC GTTGGGTAGA ATATTTTTTT GAAGATTATA ATAAAATAAA 7020ACATAAAATT TCACATCGCA TAAAAAATGG TGAAATATCT CCATGTATAA AAAATTGTGT 7080AGAAAAATGG GTAGATCAGA AAAGAAAAGA ATGGAAGGAA ATTACTGAAC GTTTCAAAGA 7140TCAATATAAA AATGACAATT CAGATGATGA CAATGTGAGA AGTTTTTTGG AGACCTTGAT 7200ACCTCAAATT ACTGATGCAA ACGCTAAAAA TAAGGTTATA AAATTAAGTA AGTTCGGTAA 7260TTCTTGTGGA TGTAGTGCCA GTGCGAACGA ACAAAACAAA AATGGTGAAT ACAAGGACGC 7320TATAGATTGT ATGCTTAAAA AGCTTAAAGA TAAAATTGGC GAGTGCGAAA AGAAACACCA 7380TCAAACTAGT GATACCGAGT GTTCCGACAC ACCACAACCG CAAACCCTTG AAGACGAAAC 7440TTTGGATGAT GATATAGAAA CAGAGGAGGC GAAGAAGAAC ATGATGCCGA AAATTTGTGA 7500AAATGTGTTA AAAACAGCAC AACAAGAGGA TGAAGGCGGT TGTGTCCCAG CAGAAAATAG 7560TGAAGAACCG GCAGCAACAG ATAGTGGTAA GGAAACCCCC GAACAAACCC CCGTTCTCAA 7620ACCCGAAGAA GAAGCAGTAC CGGAACCACC ACCTCCACCC CCACAGGAAA AAGCCCCGGC 7680ACCAATACCC CAACCACAAC CACCAACCCC CCCCACACAA CTCTTGGATA ATCCCCACGT 7740TCTAACCGCC CTGGTGACCT CCACCCTCGC CTGGAGCGTT GGCATCGGTT TTGCTACATT 7800CACTTATTTT TATCTAAAGG TAAATGGAAG TATATATATG GGGATGTGGA TGTATGTGGA 7860TGTATGTGAA TGTATGTGGA TGTATGTGGA TGTATGTGGA TGTGTTTTAT GGATATGTAT 7920TTGTGATTAT GTTTGGATAT ATATATATAT ATATATATGT TTATGTATAT GTGTTTTTGG 7980ATATATATAT GTGTATGTAT ATGATTTTCT GTATATGTAT TTGTGGGTTA AGGATATATA 8040TATATGGATG TACTTGTATG TGTTTTATAT ATATATTTTA TATATATGTA TTTATATTAA 8100AAAAGAAATA TAAAAACAAA TTTATTAAAA TGAAAAAAAG AAAAATGAAA TATAAAAAAA 8160AATTTATTAA AATAAAAAAA AAAAAAAAAA AAAAGGAGAA AAATTTTTTA AAAAATAATA 8220(2)SEQ ID NO:12资料:(I)序列特征:
(A)长度:2710个氨基酸
(B)类型:氨基酸
(C)链型:单链
(D)拓扑:线型(II)分子类型:蛋白质(III)假定的:非(VI)原始来源:
(A)生物:镰状疟原虫(XI)序列描述:SEQ ID NO:12:Asn Val Met Val Glu Leu Ala Lys Met Gly Pro Lys Glu Ala Ala Gly1 5 10 15Gly Asp Asp Ile Glu Asp Glu Ser Ala Lys His Met Phe Asp Arg Ile
20 25 30Gly Lys Asp Val Tyr Asp Lys Val Lys Glu Glu Ala Lys Glu Arg Gly
35 40 45Lys Gly Leu Gln Gly Arg Leu Ser Glu Ala Lys Phe Glu Lys Asn Glu
50 55 60Ser Asp Pro Gln Thr Pro Glu Asp Pro Cys Asp Leu Asp His Lys Tyr65 70 75 80His Thr Asn Val Thr Thr Asn Val Ile Asn Pro Cys Ala Asp Arg Ser
85 90 95Asp Val Arg Phe Ser Asp Glu Tyr Gly Gly Gln Cys Thr His Asn Arg
100 105 110Ile Lys Asp Ser Gln Gln Gly Asp Asn Lys Gly Ala Cys Ala Pro Tyr
115 120 125Arg Arg Leu His Val Cys Asp Gln Asn Leu Glu Gln Ile Glu Pro Ile
130 135 140Lys Ile Thr Asn Thr His Asn Leu Leu Val Asp Val Cys Met Ala Ala145 150 155 160Lys Phe Glu Gly Gln Ser Ile Thr Gln Asp Tyr Pro Lys Tyr Gln Ala
165 170 175Thr Tyr Gly Asp Ser Pro Ser Gln Ile Cys Thr Met Leu Ala Arg Ser
180 185 190Phe Ala Asp Ile Gly Asp Ile Val Arg Gly Arg Asp Leu Tyr Leu Gly
195 200 205Asn Pro Gln Glu Ile Lys Gln Arg Gln Gln Leu Glu Asn Asn Leu Lys
210 215 220Thr Ile Phe Gly Lys Ile Tyr Glu Lys Leu Asn Gly Ala Glu Ala Arg225 230 235 240Tyr Gly Asn Asp Pro Glu Phe Phe Lys Leu Arg Glu Asp Trp Trp Thr
245 250 255Ala Asn Arg Glu Thr Val Trp Lys Ala Ile Thr Cys Asn Ala Trp Gly
260 265 270Asn Thr Tyr Phe His Ala Thr Cys Asn Arg Gly Glu Arg Thr Lys Gly
275 280 285Tyr Cys Arg Cys Asn Asp Asp Gln Val Pro Thr Tyr Phe Asp Tyr Val
290 295 300Pro Gln Tyr Leu Arg Trp Phe Glu Glu Trp Ala Glu Asp Phe Cys Arg305 310 315 320Lys Lys Asn Lys Lys Ile Lys Asp Val Lys Arg Asn Cys Arg Gly Lys
325 330 335Asp Lys Glu Asp Lys Asp Arg Tyr Cys Ser Arg Asn Gly Tyr Asp Cys
340 345 350Glu Lys Thr Lys Arg Ala Ile Gly Lys Leu Arg Tyr Gly Lys Gln Cys
355 360 365Ile Ser Cys Leu Tyr Ala Cys Asn Pro Tyr Val Asp Trp Ile Asn Asn
370 375 380Gln Lys Glu Gln Phe Asp Lys Gln Lys Lys Lys Tyr Asp Glu Glu Ile385 390 395 400Lys Lys Tyr Glu Asn Gly Ala Ser Gly Gly Ser Arg Gln Lys Arg Asp
405 410 415Ala Gly Gly Thr Thr Thr Thr Asn Tyr Asp Gly Tyr Glu Lys Lys Phe
420 425 430Tyr Asp Glu Leu Asn Lys Ser Glu Tyr Arg Thr Val Asp Lys Phe Leu
435 440 445Glu Lys Leu Ser Asn Glu Glu Ile Cys Thr Lys Val Lys Asp Glu Glu
450 455 460Gly Gly Thr Ile Asp Phe Lys Asn Val Asn Ser Asp Ser Thr Ser Gly465 470 475 480Ala Ser Gly Thr Asn Val Glu Ser Gln Gly Thr Phe Tyr Arg Ser Lys
485 490 495Tyr Cys Gln Pro Cys Pro Tyr Cys Gly Val Lys Lys Val Asn Asn Gly
500 505 510Gly Ser Ser Asn Glu Trp Glu Glu Lys Asn Asn Gly Lys Cys Lys Ser
515 520 525Gly Lys Leu Tyr Glu Pro Lys Pro Asp Lys Glu Gly Thr Thr Ile Thr
530 535 540Ile Leu Lys Ser Gly Lys Gly His Asp Asp Ile Glu Glu Lys Leu Asn545 550 555 560Lys Phe Cys Asp Glu Lys Asn Gly Asp Thr Ile Asn Ser Gly Gly Ser
565 570 575Gly Thr Gly Gly Ser Gly Gly Gly Asn Ser Gly Arg Gln Glu Leu Tyr
580 585 590Glu Glu Trp Lys Cys Tyr Lys Gly Glu Asp Val Val Lys Val Gly His
595 600 605Asp Glu Asp Asp Glu Glu Asp Tyr Glu Asn Val Lys Asn Ala Gly Gly
610 615 620Leu Cys Ile Leu Lys Asn Gln Lys Lys Asn Lys Glu Glu Gly Gly Asn625 630 635 640Thr Ser Glu Lys Glu Pro Asp Glu Ile Gln Lys Thr Phe Asn Pro Phe
645 650 655Phe Tyr Tyr Trp Val Ala His Met Leu Lys Asp Ser Ile His Trp Lys
660 665 670Lys Lys Leu Gln Arg Cys Leu Gln Asn Gly Asn Arg Ile Lys Cys Gly
675 680 685Asn Asn Lys Cys Asn Asn Asp Cys Glu Cys Phe Lys Arg Trp Ile Thr
690 695 700Gln Lys Lys Asp Glu Trp Gly Lys Ile Val Gln His Phe Lys Thr Gln705 710 715 720Asn Ile Lys Gly Arg Gly Gly Ser Asp Asn Thr Ala Glu Leu Ile Pro
725 730 735Phe Asp His Asp Tyr Val Leu Gln Tyr Asn Leu Gln Glu Glu Phe Leu
740 745 750Lys Gly Asp Ser Glu Asp Ala Ser Glu Glu Lys Ser Glu Asn Ser Leu
755 760 765Asp Ala Glu Glu Ala Glu Glu Leu Lys His Leu Arg Glu Ile Ile Glu
770 775 780Ser Glu Asp Asn Asn Gln Glu Ala Ser Val Gly Gly Gly Val Thr Glu785 790 795 800Gln Lys Asn Ile Met Asp Lys Leu Leu Asn Tyr Glu Lys Asp Glu Ala
805 810 815Asp Leu Cys Leu Glu Ile His Glu Asp Glu Glu Glu Glu Lys Glu Lys
820 825 830Gly Asp Gly Asn Glu Cys Ile Glu Glu Gly Glu Asn Phe Arg Tyr Asn
835 840 845Pro Cys Ser Gly Glu Ser Gly Asn Lys Arg Tyr Pro Val Leu Ala Asn
850 855 860Lys Val Ala Tyr Gln Met His His Lys Ala Lys Thr Gln Leu Ala Ser865 870 875 880Arg Ala Gly Arg Ser Ala Leu Arg Gly Asp Ile Ser Leu Ala Gln Phe
885 890 895Lys Asn Gly Arg Asn Gly Ser Thr Leu Lys Gly Gln Ile Cys Lys Ile
900 905 910Asn Glu Asn Tyr Ser Asn Asp Ser Arg Gly Asn Ser Gly Gly Pro Cys
915 920 925Thr Gly Lys Asp Gly Asp His Gly Gly Val Arg Met Arg Ile Gly Thr
930 935 940Glu Trp Ser Asn Ile Glu Gly Lys Lys Gln Thr Ser Tyr Lys Asn Val945 950 955 960Phe Leu Pro Pro Arg Arg Glu His Met Cys Thr Ser Asn Leu Glu Asn
965 970 975Leu Asp Val Gly Ser Val Thr Lys Asn Asp Lys Ala Ser His Ser Leu
980 985 990Leu Gly Asp Val Gln Leu Ala Ala Lys Thr Asp Ala Ala Glu Ile Ile
995 1000 1005Lys Arg Tyr Lys Asp Gln Asn Asn Ile Gln Leu Thr Asp Pro Ile Gln
1010 1015 1020Gln Lys Asp Gln Glu Ala Met Cys Arg Ala Val Arg Tyr Ser Phe Ala1025 1030 1035 1040Asp Leu Gly Asp Ile Ile Arg Gly Arg Asp Met Trp Asp Glu Asp Lys
1045 1050 1055Ser Ser Thr Asp Met Glu Thr Arg Leu Ile Thr Val Phe Lys Asn Ile
1060 1065 1070Lys Glu Lys His Asp Gly Ile Lys Asp Asn Pro Lys Tyr Thr Gly Asp
1075 1080 1085Glu Ser Lys Lys Pro Ala Tyr Lys Lys Leu Arg Ala Asp Trp Trp Glu
1090 1095 1100Ala Asn Arg His Gln Val Trp Arg Ala Met Lys Cys Ala Thr Lys Gly1105 1110 1115 1120Ile Ile Cys Pro Gly Met Pro Val Asp Asp Tyr Ile Pro Gln Arg Leu
1125 1130 1135Arg Trp Met Thr Glu Trp Ala Glu Trp Tyr Cys Lys Ala Gln Ser Gln
1140 1145 1150Glu Tyr Asp Lys Leu Lys Lys Ile Cys Ala Asp Cys Met Ser Lys Gly
1155 1160 1165Asp Gly Lys Cys Thr Gln Gly Asp Val Asp Cys Gly Lys Cys Lys Ala
1170 1175 1180Ala Cys Asp Lys Tyr Lys Glu Glu Ile Glu Lys Trp Asn Glu Gln Trp1185 1190 1195 1200Arg Lys Ile Ser Asp Lys Tyr Asn Leu Leu Tyr Leu Gln Ala Lys Thr
1205 1210 1215Thr Ser Thr Asn Pro Gly Arg Thr Val Leu Gly Asp Asp Asp Pro Asp
1220 1225 1230Tyr Gln Gln Met Val Asp Phe Leu Thr Pro Ile His Lys Ala Ser Ile
1235 1240 1245Ala Ala Arg Val Leu Val Lys Arg Ala Ala Gly Ser Pro Thr Glu Ile
1250 1255 1260Ala Ala Ala Ala Pro Ile Thr Pro Tyr Ser Thr Ala Ala Gly Tyr Ile1265 1270 1275 1280His Gln Glu Ile Gly Tyr Gly Gly Cys Gln Glu Gln Thr Gln Phe Cys
1285 1290 1295Glu Lys Lys His Gly Ala Thr Ser Thr Ser Thr Thr Lys Glu Asn Lys
1300 1305 1310Glu Tyr Thr Phe Lys Gln Pro Pro Pro Glu Tyr Ala Thr Ala Cys Asp
1315 1320 1325Cys Ile Asn Arg Ser Gln Thr Glu Glu Pro Lys Lys Lys Glu Glu Asn
1330 1335 1340Val Glu Ser Ala Cys Lys Ile Val Glu Lys Ile Leu Glu Gly Lys Asn1345 1350 1355 1360Gly Arg Thr Thr Val Gly Glu Cys Asn Pro Lys Glu Ser Tyr Pro Asp
1365 1370 1375Trp Asp Cys Lys Asn Asn Ile Asp Ile Ser His Asp Gly Ala Cys Met
1380 1385 1390Pro Pro Arg Arg Gln Lys Leu Cys Leu Tyr Tyr Ile Ala His Glu Ser
1395 1400 1405Gln Thr Glu Asn Ile Lys Thr Asp Asp Asn Leu Lys Asp Ala Phe Ile
1410 1415 1420Lys Thr Ala Ala Ala Glu Thr Phs Leu Ser Trp Gln Tyr Tyr Lys Ser1425 1430 1435 1440Lys Asn Asp Ser Glu Ala Lys Ile Leu Asp Arg Gly Leu Ile Pro Ser
1445 1450 1455Gln Phe Leu Arg Ser Met Met Tyr Thr Phe Gly Asp Tyr Arg Asp Ile
1460 1465 1470Cys Leu Asn Thr Asp Ile Ser Lys Lys Gln Asn Asp Val Ala Lys Ala
1475 1480 1485Lys Asp Lys Ile Gly Lys Phe Phe Ser Lys Asp Gly Ser Lys Ser Pro
1490 1495 1500Ser Gly Leu Ser Arg Gln Glu Trp Trp Lys Thr Asn Gly Pro Glu Ile1505 1510 1515 1520Trp Lys Gly Met Leu Cys Ala Leu Thr Lys Tyr Val Thr Asp Thr Asp
1525 1530 1535Asn Lys Arg Lys Ile Lys Asn Asp Tyr Ser Tyr Asp Lys Val Asn Gln
1540 1545 1550Ser Gln Asn Gly Asn Pro Ser Leu Glu Glu Phe Ala Ala Lys Pro Gln
1555 1560 1565Phe Leu Arg Trp Met Ile Glu Trp Gly Glu Glu Phe Cys Ala Glu Arg
1570 1575 1580Gln Lys Lys Glu Asn Ile Ile Lys Asp Ala Cys Asn Glu Ile Asn Ser1585 1590 1595 1600Thr Gln Gln Cys Asn Asp Ala Lys His Arg Cys Asn Gln Ala Cys Arg
1605 1610 1615Ala Tyr Gln Glu Tyr Val Glu Asn Lys Lys Lys Glu Phe Ser Gly Gln
1620 1625 1630Thr Asn Asn Phe Val Leu Lys Ala Asn Val Gln Pro Gln Asp Pro Glu
1635 1640 1645Tyr Lys Gly Tyr Glu Tyr Lys Asp Gly Val Gln Pro Ile Gln Gly Asn
1650 1655 1660Glu Tyr Leu Leu Gln Lys Cys Asp Asn Asn Lys Cys Ser Cys Met Asp1665 1670 1675 1680Gly Asn Val Leu Ser Val Ser Pro Lys Glu Lys Pro Phe Gly Lys Tyr
1685 1690 1695Ala His Lys Tyr Pro Glu Lys Cys Asp Cys Tyr Gln Gly Lys His Val
1700 1705 1710Pro Ser Ile Pro Pro Pro Pro Pro Pro Val Gln Pro Gln Pro Glu Ala
1715 1720 1725Pro Thr Val Thr Val Asp Val Cys Ser Ile Val Lys Thr Leu Phe Lys
1730 1735 1740Asp Thr Asn Asn Phe Ser Asp Ala Cys Gly Leu Lys Tyr Gly Lys Thr1745 1750 1755 1760Ala Pro Ser Ser Trp Lys Cys Ile Pro Ser Asp Thr Lys Ser Gly Ala
1765 1770 1775Gly Ala Thr Thr Gly Lys Ser Gly Ser Asp Ser Gly Ser Ile Cys Ile
1780 1785 1790Pro Pro Arg Arg Arg Arg Leu Tyr Val Gly Lys Leu Gln Glu Trp Ala
1795 1800 1805Thr Ala Leu Pro Gln Gly Glu Gly Ala Ala Pro Ser His Ser Arg Ala
1810 1815 1820Asp Asp Leu Arg Asn Ala Phe Ile Gln Ser Ala Ala Ile Glu Thr Phe1825 1830 1835 1840Phe Leu Trp Asp Arg Tyr Lys Glu Glu Lys Lys Pro Gln Gly Asp Gly
1845 1850 1855Ser Gln Gln Ala Leu Ser Gln Leu Thr Ser Thr Tyr Ser Asp Asp Glu
1860 1865 1870Glu Asp Pro Pro Asp Lys Ieu Leu Gln Asn Gly Lys Ile Pro Pro Asp
1875 1880 1885Phe Leu Arg Leu Met Phe Tyr Thr Leu Gly Asp Tyr Arg Asp Ile Leu
1890 1895 1900Val His Gly Gly Asn Thr Ser Asp Ser Gly Asn Thr Asn Gly Ser Asn1905 1910 1915 1920Asn Asn Asn Ile Val Leu Glu Ala Ser Gly Asn Lys Glu Asp Met Gln
1925 1930 1935Lys Ile Gln Glu Lys Ile Glu Gln Ile Leu Pro Lys Asn Gly Gly Thr
1940 1945 1950Pro Leu Val Pro Lys Ser Ser Ala Gln Thr Pro Asp Lys Trp Trp Asn
1955 1960 1965Glu His Ala Glu Ser Ile Trp Lys Gly Met Ile Cys Ala Leu Thr Tyr
1970 1975 1980Thr Glu Lys Asn Pro Asp Thr Ser Ala Arg Gly Asp Glu Asn Lys Ile1985 1990 1995 2000Glu Lys Asp Asp Glu Val Tyr Glu Lys Phe Phe Gly Ser Thr Ala Asp
2005 2010 2015Lys His Gly Thr Ala Ser Thr Pro Thr Gly Thr Tyr Lys Thr Gln Tyr
2020 2025 2030Asp Tyr Glu Lys Val Lys Leu Glu Asp Thr Ser Gly Ala Lys Thr Pro
2035 2040 2045Ser Ala Ser Ser Asp Thr Pro Leu Leu Ser Asp Phe Val Leu Arg Pro
2050 2055 2060Pro Tyr Phe Arg Tyr Leu Glu Glu Trp Gly Gln Asn Phe Cys Lys Lys2065 2070 2075 2080Arg Lys His Lys Leu Ala Gln Ile Lys His Glu Cys Lys Val Glu Glu
2085 2090 2095Asn Gly Gly Gly Ser Arg Arg Gly Gly Ile Thr Arg Gln Tyr Ser Gly
2100 2105 2110Asp Gly Glu Ala Cys Asn Glu Met Leu Pro Lys Asn Asp Gly Thr Val
2115 2120 2125Pro Asp Leu Glu Lys Pro Ser Cys Ala Lys Pro Cys Ser Ser Tyr Arg
2130 2135 2140Lys Trp Ile Glu Ser Lys Gly Lys Glu Phe Glu Lys Gln Glu Lys Ala2145 2150 2155 2160Tyr Glu Gln Gln Lys Asp Lys Cys Val Asn Gly Ser Asn Lys His Asp
2165 2170 2175Asn Gly Phe Cys Glu Thr Leu Thr Thr Ser Ser Lys Ala Lys Asp Phe
2180 2185 2190Leu Lys Thr Leu Gly Pro Cys Lys Pro Asn Asn Val Glu Gly Lys Thr
2195 2200 2205Ile Phe Asp Asp Asp Lys Thr Phe Lys His Thr Lys Asp Cys Asp Pro
2210 2215 2220Cys Leu Lys Phe Ser Val Asn Cys Lys Lys Asp Glu Cys Asp Asn Ser2225 2230 2235 2240Lys Gly Thr Asp Cys Arg Asn Lys Asn Ser Ile Asp Ala Thr Asp Ile
2245 2250 2255Glu Asn Gly Val Asp Ser Thr Val Leu Glu Met Arg Val Ser Ala Asp
2260 2265 2270Ser Lys Ser Gly Phe Asn Gly Asp Gly Leu Glu Asn Ala Cys Arg Gly
2275 2280 2285Ala Gly Ile Phe Glu Gly Ile Arg Lys Asp Glu Trp Lys Cys Arg Asn
2290 2295 2300Val Cys Gly Tyr Val Val Cys Lys Pro Glu Asn Val Asn Gly Glu Ala2305 2310 2315 2320Lys Gly Lys His Ile Ile Gln Ile Arg Ala Leu Val Lys Arg Trp Val
2325 2330 2335Glu Tyr Phe Phe Glu Asp Tyr Asn Lys Ile Lys His Lys Ile Ser His
2340 2345 2350Arg Ile Lys Asn Gly Glu Ile Ser Pro Cys Ile Lys Asn Cys Val Glu
2355 2360 2365Lys Trp Val Asp Gln Lys Arg Lys Glu Trp Lys Glu Ile Thr Glu Arg
2370 2375 2380Phe Lys Asp Gln Tyr Lys Asn Asp Asn Ser Asp Asp Asp Asn Val Arg2385 2390 2395 2400Ser Phe Leu Glu Thr Leu Ile Pro Gln Ile Thr Asp Ala Asn Ala Lys
2405 2410 2415Asn Lys Val Ile Lys Leu Ser Lys Phe Gly Asn Ser Cys Gly Cys Ser
2420 2425 2430Ala Ser Ala Asn Glu Gln Asn Lys Asn Gly Glu Tyr Lys Asp Ala Ile
2435 2440 2445Asp Cys Met Leu Lys Lys Leu Lys Asp Lys Ile Gly Glu Cys Glu Lys
2450 2455 2460Lys His His Gln Thr Ser Asp Thr Glu Cys Ser Asp Thr Pro Gln Pro2465 2470 2475 2480Gln Thr Leu Glu Asp Glu Thr Leu Asp Asp Asp Ile Glu Thr Glu Glu
2485 2490 2495Ala Lys Lys Asn Met Met Pro Lys Ile Cys Glu Asn Val Leu Lys Thr
2500 2505 2510Ala Gln Gln Glu Asp Glu Gly Gly Cys Val Pro Ala Glu Asn Ser Glu
2515 2520 2525Glu Pro Ala Ala Thr Asp Ser Gly Lys Glu Thr Pro Glu Gln Thr Pro
2530 2535 2540Val Leu Lys Pro Glu Glu Glu Ala Val Pro Glu Pro Pro Pro Pro Pro2545 2550 2555 2560Pro Gln Glu Lys Ala Pro Ala Pro Ile Pro Gln Pro Gln Pro Pro Thr
2565 2570 2575Pro Pro Thr Gln Leu Leu Asp Asn Pro His Val Leu Thr Ala Leu Val
2580 2585 2590Thr Ser Thr Leu Ala Trp Ser Val Gly Ile Gly Phe Ala Thr Phe Thr
2595 2600 2605Tyr Phe Tyr Leu Lys Val Asn Gly Ser Ile Tyr Met Gly Met Trp Met
2610 2615 2620Tyr Val Asp Val Cys Glu Cys Met Trp Met Tyr Val Asp Val Cys Gly2625 2630 2635 2640Cys Val Leu Trp Ile Cys Ile Cys Asp Tyr Val Trp Ile Tyr Ile Tyr
2645 2650 2655Ile Tyr Ile Cys Leu Cys Ile Cys Val Phe Gly Tyr Ile Tyr Val Tyr
2660 2665 2670Val Tyr Asp Phe Leu Tyr Met Tyr Leu Trp Val Lys Asp Ile Tyr Ile
2675 2680 2685Trp Met Tyr Leu Tyr Val Phe Tyr Ile Tyr Ile Leu Tyr Ile Cys Ile
2690 2695 2700Tyr Ile Lys Lys Glu Ile2705 2710
Claims (29)
1.一种组合物,包含分离的DABP结合区多肽。
2.权利要求1的组合物,其中DABP结合区多肽包含大约200到大约300之间的氨基酸残基。
3.权利要求1的组合物,其中的DABP结合区多肽具有SEQ ID NO.2的残基1到大约325的氨基酸序列。
4.权利要求1的组合物,其中的DABP结合区多肽是经重组产生的。
5.一种药物组合物,包含药学用上可接受的载体和是以诱导生物抗间日疟原虫裂殖子的保护性免疫应答量分离的DABP结合区多肽。
6.权利要求5的组合物,还包含以足以诱导生物抗镰状疟原虫裂殖子的保护性免疫应答量的分离的SABP结合区多肽。
7.一种组合物,包含分离的SABP结合区多肽。
8.权利要求7的组合物,其中的SABP结合区多肽含大约200到大约600之间的氨基酸残基。
9.权利要求7的组合物,其中的SABP结合区多肽具有SEQ ID NO.4的残基1到大约616的氨基酸序列。
10.权利要求7的组合物,其中的SABP结合区多肽是重组产生的。
11.一种药物组合物,含有药学用上可接受的载体和足以诱导生物抗镰状疟原虫裂殖子保护性免疫应答量的分离的SABP结合区多肽。
12.权利要求11的组合物,进一步包含以足以诱导生物抗间日疟原虫裂殖子的保护性免疫应答量的分离的DABP结合区多肽。
13.一种组合物,包含分离的编码DABP结合区多肽的多核甙酸。
14.权利要求13的组合物,其中的多核苷酸编码具有SEQ ID NO.2残基1到大约325的氨基酸序列的DABP结合区多肽。
15.一种重组细胞,包含权利要求13的多核苷酸。
16.一种组合物,包含分离的编码SABP结合区多肽的多核苷酸。
17.权利要求16的组合物,其中的多核苷酸编码具有SEQ ID NO.4残基1到大约616的氨基酸序列的SABP结合区多肽。
18.一种重组细胞,含有权利要求16的多核苷酸。
19.一种诱导患者抗疟原虫属裂殖子的保护性免疫应答的方法,该方法包含给病人施用免疫有效量的药物组合物,该组合物包含药学上可接受的载体和分离的多肽,该多肽选自由DABP结合区多肽,SABP结合区多肽和两者结合组成的组中。
20.权利要求19的方法,其中的患者是人类。
21.一种组合物,包含EBL基因家族的核苷酸序列。
22.一种组合物,包含ebl-e1基因的核酸序列。
23.权利要求22的组合物,其中的ebl-e1基因具有SEQ ID NO.5的核苷酸序列。
24.一种组合物,含有E31a基因的核苷酸序列。
25.权利要求24的组合物,其中的E31a基因具有SEQID NO.7的核苷酸序列。
26.一种组合物,含有Proj3基因的核苷酸序列。
27.权利要求26的组合物,其中的Proj3基因具有SEQID NO.11的核苷酸序列。
28.一种组合物,含有EBL-e2基因的核苷酸序列。
29.权利要求28的组合物,其中EBL-e2基因具有SEQ ID NO.9的核苷酸序列。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US11967793A | 1993-09-10 | 1993-09-10 | |
US08/119,677 | 1993-09-10 |
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CN02131950A Division CN1414018A (zh) | 1993-09-10 | 2002-09-05 | 间日疟原虫和镰状疟原虫红细胞结合蛋白的结合区 |
CN02131951A Division CN1414102A (zh) | 1993-09-10 | 2002-09-05 | 间日疟原虫和镰状疟原虫红细胞结合蛋白的结合区 |
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CN1134173A true CN1134173A (zh) | 1996-10-23 |
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CN94193335A Pending CN1134173A (zh) | 1993-09-10 | 1994-09-07 | 间日疟原虫和镰状疟原虫红细胞结合蛋白的结合区 |
CN02131950A Pending CN1414018A (zh) | 1993-09-10 | 2002-09-05 | 间日疟原虫和镰状疟原虫红细胞结合蛋白的结合区 |
CN02131951A Pending CN1414102A (zh) | 1993-09-10 | 2002-09-05 | 间日疟原虫和镰状疟原虫红细胞结合蛋白的结合区 |
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CN02131950A Pending CN1414018A (zh) | 1993-09-10 | 2002-09-05 | 间日疟原虫和镰状疟原虫红细胞结合蛋白的结合区 |
CN02131951A Pending CN1414102A (zh) | 1993-09-10 | 2002-09-05 | 间日疟原虫和镰状疟原虫红细胞结合蛋白的结合区 |
Country Status (10)
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US (3) | US5849306A (zh) |
EP (1) | EP0719333B1 (zh) |
JP (1) | JPH09502353A (zh) |
CN (3) | CN1134173A (zh) |
AT (1) | ATE286536T1 (zh) |
AU (1) | AU694142B2 (zh) |
CA (1) | CA2171193A1 (zh) |
DE (1) | DE69434221T2 (zh) |
HK (1) | HK1010395A1 (zh) |
WO (1) | WO1995007353A2 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN110343161A (zh) * | 2019-07-30 | 2019-10-18 | 暨南大学 | 一种检测恶性疟原虫hrp2和间日疟原虫ldh的结合蛋白组合及其制备方法和应用 |
Families Citing this family (16)
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CA2171193A1 (en) * | 1993-09-10 | 1995-03-16 | Kim Lee Sim | Binding domains from plasmodium vivax and plasmodium falciparum erythrocyte binding proteins |
US5993827A (en) * | 1993-09-10 | 1999-11-30 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Binding domains from plasmodium vivax and plasmodium falciparum erythrocyte binding proteins |
US6346510B1 (en) | 1995-10-23 | 2002-02-12 | The Children's Medical Center Corporation | Therapeutic antiangiogenic endostatin compositions |
SE9703386D0 (sv) * | 1997-09-19 | 1997-09-19 | Karolinska Innovations Ab | Malaria polypeptides |
US7459524B1 (en) | 1997-10-02 | 2008-12-02 | Emergent Product Development Gaithersburg Inc. | Chlamydia protein, sequence and uses thereof |
US7025961B1 (en) | 1999-03-04 | 2006-04-11 | The United States Of America As Represented By The Department Of Health And Human Services | Anti-plasmodium composition and methods of use |
WO2000052056A2 (en) * | 1999-03-04 | 2000-09-08 | Entremed, Inc. | Anti-plasmodium compositions and methods of use |
AU2004201615B2 (en) * | 1999-03-04 | 2007-01-25 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Anti-plasmodium compositions and methods of use |
AU2001281140A1 (en) * | 2000-08-07 | 2002-02-18 | Entremed, Inc | Anti-plasmodium compositions and methods of use |
WO2002078603A2 (en) * | 2001-04-02 | 2002-10-10 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Plasmodium falciparum erythrocyte binding protein baebl for use as a vaccine |
US7041808B2 (en) * | 2001-10-15 | 2006-05-09 | National Institute Of Agrobiological Sciences | Antimicrobial proteins, genes encoding the proteins and method of using the same |
WO2003062374A2 (en) * | 2001-11-09 | 2003-07-31 | Entremed, Inc. | Synthetic genes for malarial proteins and methods of use |
NZ574239A (en) * | 2006-07-18 | 2011-12-22 | Glaxosmithkline Biolog Sa | Hybrid fusion proteins for malaria vaccines |
US7773575B2 (en) * | 2006-07-24 | 2010-08-10 | Harris Corporation | System and method for communicating using a plurality of TDMA mesh networks having efficient bandwidth use |
CN101921337B (zh) * | 2010-07-21 | 2013-05-08 | 上海市疾病预防控制中心 | 间日疟原虫乳酸脱氢酶抗体、相关制备方法、杂交瘤细胞株和应用 |
US8784832B2 (en) * | 2011-08-19 | 2014-07-22 | University Of South Florida (A Florida Non-Profit Corporation) | Synthetic antigen based on the ligand domain of the Plasmodium vivax duffy binding protein |
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US5144007A (en) * | 1988-11-03 | 1992-09-01 | La Jolla Cancer Research Foundation | Thyroid hormone receptor |
US5198347A (en) * | 1990-07-20 | 1993-03-30 | The United States Of America As Represented By The Department Of Health And Human Services | Dna encoding plasmodium vivax and plasmodium knowlesi duffy receptor |
WO1993018160A1 (en) * | 1992-03-11 | 1993-09-16 | Kenneth Francis Prendergast | Anti-viral fusion peptides |
CA2171193A1 (en) * | 1993-09-10 | 1995-03-16 | Kim Lee Sim | Binding domains from plasmodium vivax and plasmodium falciparum erythrocyte binding proteins |
US5993827A (en) * | 1993-09-10 | 1999-11-30 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Binding domains from plasmodium vivax and plasmodium falciparum erythrocyte binding proteins |
-
1994
- 1994-09-07 CA CA002171193A patent/CA2171193A1/en not_active Abandoned
- 1994-09-07 AT AT94929779T patent/ATE286536T1/de not_active IP Right Cessation
- 1994-09-07 DE DE69434221T patent/DE69434221T2/de not_active Expired - Fee Related
- 1994-09-07 WO PCT/US1994/010230 patent/WO1995007353A2/en active IP Right Grant
- 1994-09-07 CN CN94193335A patent/CN1134173A/zh active Pending
- 1994-09-07 JP JP7508825A patent/JPH09502353A/ja active Pending
- 1994-09-07 EP EP94929779A patent/EP0719333B1/en not_active Expired - Lifetime
- 1994-09-07 AU AU78721/94A patent/AU694142B2/en not_active Revoked
-
1995
- 1995-12-07 US US08/568,459 patent/US5849306A/en not_active Expired - Fee Related
-
1998
- 1998-10-05 HK HK98111108A patent/HK1010395A1/xx not_active IP Right Cessation
- 1998-12-11 US US09/210,288 patent/US6392026B1/en not_active Expired - Fee Related
-
2002
- 2002-05-21 US US10/153,273 patent/US6962987B2/en not_active Expired - Fee Related
- 2002-09-05 CN CN02131950A patent/CN1414018A/zh active Pending
- 2002-09-05 CN CN02131951A patent/CN1414102A/zh active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110343161A (zh) * | 2019-07-30 | 2019-10-18 | 暨南大学 | 一种检测恶性疟原虫hrp2和间日疟原虫ldh的结合蛋白组合及其制备方法和应用 |
CN110343161B (zh) * | 2019-07-30 | 2021-08-20 | 暨南大学 | 一种检测恶性疟原虫hrp2和间日疟原虫ldh的结合蛋白组合及其制备方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
AU7872194A (en) | 1995-03-27 |
CN1414102A (zh) | 2003-04-30 |
DE69434221D1 (de) | 2005-02-10 |
US5849306A (en) | 1998-12-15 |
JPH09502353A (ja) | 1997-03-11 |
AU694142B2 (en) | 1998-07-16 |
ATE286536T1 (de) | 2005-01-15 |
DE69434221T2 (de) | 2006-01-19 |
US20020169305A1 (en) | 2002-11-14 |
US6962987B2 (en) | 2005-11-08 |
EP0719333B1 (en) | 2005-01-05 |
WO1995007353A2 (en) | 1995-03-16 |
CA2171193A1 (en) | 1995-03-16 |
WO1995007353A3 (en) | 1995-06-01 |
CN1414018A (zh) | 2003-04-30 |
HK1010395A1 (en) | 1999-06-17 |
US6392026B1 (en) | 2002-05-21 |
EP0719333A1 (en) | 1996-07-03 |
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