CN1784220A - 谷氨酰胺酰基和谷氨酸环化酶效应物的应用 - Google Patents
谷氨酰胺酰基和谷氨酸环化酶效应物的应用 Download PDFInfo
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Abstract
Description
氨基酸 | 单字母符号 | 三字母符号 |
甘氨酸精氨酸天冬酰胺天冬氨酸半胱氨酸谷氨酰胺谷氨酸甘氨酸组氨酸异亮氨酸亮氨酸赖氨酸甲硫氨酸苯丙氨酸脯氨酸丝氨酸苏氨酸色氨酸酪氨酸缬氨酸 | ARNDCQEGHILKMFPSTWYV | AlaArgAsnAspCysGlnGluGlyHisIleLeuLysMetPheProSerThrTrpTyrVal |
底物 | 人QC | 木瓜QC | ||||
KM(μM) | Kcat(s-1) | Kcat/KM(mM-1s-1) | KM(μM) | Kcat(s-1) | Kcat/KM(mM-1s-1) | |
[Gln1]-胃泌素 | 31±1 | 54.1±1.6 | 1745.2±36.9 | 34±2 | 25.8±0.5 | 759±30 |
[Gln1]-神经降压肽 | 37±1 | 48.8±0.4 | 1318.9±24.8 | 40±3 | 35.7±0.9 | 893±44 |
[Gln1]-FPP | 87±2 | 69.6±0.3 | 800.0±14.9 | 232±9 | 32.5±0.4 | 140±4 |
[Gln1]-TRH | 90±4 | 82.8±1.2 | 920.0±27.6 | n.d. | n.d. | n.d. |
[Gln1]-GnRH | 53±3 | 69.2±1.1 | 1305.7±53.2 | 169±9 | 82.5±1.9 | 488.2±114.8 |
[Gln3]-胰高血糖素(3-29) | * | * | ||||
[Gln5-物质P(5-11) | * | * |
肽 | 氨基酸序列 | 功能 |
胃泌素17Swiss-Prot:P01350 | QGPWL EEEEEAYGWM DF(酰胺) | 胃泌素刺激胃粘膜产生并分泌盐酸并刺激胰腺分泌消化酶。胃泌素还刺激平滑肌收缩和增加血液循环及胃肠道分泌水分。 |
神经降压肽Swiss-Prot:P30990 | QLYENKPRRP YIL | 神经降压肽在调节脂肪代谢中起内分泌或旁分泌的作用。它引起平滑肌收缩。 |
FPP | QEP酰胺 | 在精液浆中发现的与促甲状腺素释放激素(TRH)有关的三肽。最近获得的体外和体内证据表明FPP在调节精子生育能力方面起重要作用。 |
TRHSwiss-Prot:P20396 | QHP酰胺 | TRH在前脑垂体腺中起着TSH生物合成的调节剂的功能,并在中枢和外周神经系统中起着神经递质/神经调质的功能。 |
GnRHSwiss-Prot:P01148 | QHWSYGL RP(G)酰胺 | 刺激促性腺激素分泌;刺激黄体化(lutejnizing)及促卵泡激素的分泌。 |
CCL16(小的可诱导细胞因子A16)Swiss-Prot:O15467 | QPKVPEW VNTPSTCCLKYYEKVLPRRL YYGYRKALNCHLPAIIFVTK RNREVCTNPNDDWVQEYIKD PNLPLLPTRNLSTVKIITAK NGQPQLLNSQ | 对淋巴细胞和单核细胞但不对嗜中性粒细胞表现趋化活性。也表现强效的骨髓抑制(myelosuppressive)活性,抑制髓祖细胞增殖。重组SCYA16对单核细胞和THP-1单核细胞但不对静息淋巴细胞和嗜中性粒细胞表现趋化活性。诱导经预先表达RANTES脱敏的THP-1细胞的钙流。 |
CCL8(小的可诱导的细胞因子A8)Swiss-Prot:P80075 | QPDSVSI PITCCFNVINRKIPIQRLES YTRITNIQCPKEAVIFKTKR GKEVCADPKERWVRDSMKHL DQIFQNLKP | 吸引单核细胞、淋巴细胞、嗜碱细胞和嗜曙红细胞的趋化因子。可能在瘤形成和炎症宿主应答中起作用。该蛋白可结合肝素(heparin)。 |
CCL2(小的可诱导细胞因子A2)Swiss-Prot:P13500 | QPDAINA PVTCCYNFTNRKISVQRLAS YRRITSSKCPKEAVIFKTIV AKEICADPKQKWVQDSMDHL DKQTQTPKT | 吸引单核细胞和嗜碱细胞但不吸引嗜中性粒细胞或嗜曙红细胞的趋化因子。增强单核细胞的抗肿瘤活性。有涉及在以单核细胞渗透为特征的疾病如银屑病、类风湿性关节炎或动脉粥样硬化症的发病机理的迹象。可能涉及动脉粥样硬化症期间将单核细胞募集到动脉壁上。与CCR2及CCR4结合。 |
CCL18(可诱导的小细胞因子A18)Swiss-Prot:P55774 | QVGTNKELC CLVYTSWQIPQKFIVDYSET SPQCPKPGVILLTKRGRQIC ADPNKKWVQKYISDLKLNA | 吸引淋巴细胞但不吸引嗜单核细胞或粒细胞的趋化因子。可能涉及B细胞迁移进入淋巴结中的B细胞小囊内。吸引幼T淋巴细胞至淋巴结中的树枝状细胞及活化的巨噬细胞,对幼T细胞、CD4+和CD8+T细胞有趋化活性并因此可能在体液和细胞介导 |
的免疫应答中起作用。 | ||
分形素(神经趋化素,neurotactin)Swiss-Prot:P78423 | QHHGVT KCNITCSKMTSKIPVALLIH YQQNQASCGKRAIILETRQH RLFCADPKEQWVKDAMQHLD RQAAALTRNGGTFEKQIGEV KPRTTPAAGGMDESYYLEPE ATGESSSLEPTPSSQEAQRA LGTSPELPTGVTGSSGTRLP PTPKAQDGGPVGTELFRVPP VSTAATWQSSAPHQPGPSLW AEAKTSEAPSTQDPSTQAST ASSPAPEENAPSEGQRVWGQ GQSPRPENSLEREEMGPVPA HTDAFQDWGPGSMAHVSVVP VSSEGTPSREPVASGSWTPK AEEPIHATMDPQRLGVLITP VPDAQAATRRQAVGLLAFLG LLFCLGVAMFTYQSLQGCPR KMAGEMAEGLRYIPRSCGSN SYVLVPV | 可溶形式对T细胞和单核细胞但不对嗜中性粒细胞有趋化性。膜结合形式促进白细胞粘附于内皮细胞。可能在调节白细胞粘附于内皮和迁移过程中起作用。与cx3cr1结合。 |
CCL7(小的可诱导的细胞因子A7)Swiss-Prot:P80098 | QPVGINT STTCCYRFINKKIPKQRLES YRRTTSSHCPREAVIFKTKL DKEICADPTQKWVQDFMKHL DKKTQTPKL | 吸引单核细胞和嗜曙红细胞但不吸引嗜中性粒细胞的趋化因子。增强单核细胞的抗肿瘤活性。也促进白明胶酶B的释放。该蛋白可键合肝磷脂。键合于CCR1、CCR2以及CCR3。 |
胖素A(下丘泌素-1)Swiss-Prot:043612 | QPLPDCCRQK TCSCRLYELLHGAGNHAAGILTL | 可能通过协调这些互补的平衡功能的复杂行为和生理应答而在调节食物摄取和失眠中起到显著作用的神经肽。它在能量代谢、自主功能、激素平衡以及体液调节的平衡调节方面还起到更广泛的作用。胖素-A以高亲合力与OX1R及OX2R结合。 |
P物质 | RPK PQQFFGLM | 属于速激肽。速激肽是兴奋神经元、唤醒行为应答的活性肽,是强效的血管扩张剂和促分泌素,并且可以收缩(直接或间接)很多平滑肌。 |
化合物 | Ki值(mM) | 结构 |
核心结构咪唑苯并咪唑N-1衍生物1-苄基咪唑1-甲基咪唑1-乙烯基咪唑草酸二咪唑烷酰胺N-乙酰基咪唑N-(三甲基甲硅烷基)-咪唑N-苯甲酰基咪唑1-(2-氧-2-苯基-乙基)-咪唑1-(3-氨基丙基)-咪唑1-苯基咪唑1,1′-磺酰二咪唑C-4(5)衍生物N-ω-乙酰基组氨酸L-组氨酰胺H-His-Trp-OHL-组氨醇L-组氨酸4-咪唑-甲醛咪唑-4-碳酸甲酯L-组胺C-4,5衍生物5-羟甲基-4-甲基-咪唑4-氨基-咪唑-5-碳酸酰胺4,5-二苯基-咪唑4,5-二氰基咪唑C-2衍生物2-甲基-苄基咪唑2-乙基-4-甲基-咪唑2-氨基苯并咪唑2-氯-1H-苯并咪唑 | 0.103±0.0040.138±0.0050.0071±0.00030.030±0.0010.049±0.0020.078±0.0020.107±0.0030.167±0.0070.174±0.0070.184±0.0050.41±0.01无抑制作用无抑制作用0.017±0.0010.56±0.040.60±0.031.53±0.124.4±0.27.6±0.714.5±0.60.85±0.040.129±0.00515.5±0.5无抑制作用无抑制作用0.165±0.0040.58±0.041.8±0.1无抑制作用 |
底物 | 人QC | 木瓜QC | ||||||
KM(μM) | Kcat(s-1) | Ki*(mM) | kcat/KM(mM-1s-1) | KM(μM) | Kcat(s-1) | Ki*(mM) | kcat/KM(mM-1s-1) | |
H-Gln-OH | n.r. | n.r. | n.d. | n.r. | n.d. | n.d. | n.d. | 0.23±0.1 |
H-Gln-AMC | 54±2 | 5.3±0.1 | n.d. | 98±2 | 42±1 | 39.4±0.4 | n.d. | 938±13 |
H-Gln-βNA | 70±3 | 20.6±0.5 | 1.21±0.07 | 294±6 | 38±3 | 51.4±1.4 | 1.20±0.08 | 1353±70 |
H-Gln-OtBu | 1235±74 | 6.7±0.2 | n.i. | 5.4±0.2 | 223±9 | 49.4±0.6 | n.i. | 222±6 |
H-Gln-NH2 | 409±40 | 12.8±0.5 | n.i. | 31±2 | 433±13 | 44.8±0.4 | n.i. | 103±2 |
H-Gln-Gly-OH | 247±10 | 13.2±0.2 | n.i. | 53±1 | 641±20 | 45.8±0.4 | n.i. | 71±2 |
H-Gln-Ala-OH | 232±5 | 57.2±0.4 | n.i. | 247±4 | 158±8 | 69.8±1.0 | n.i. | 442±16 |
H-Gln-Gln-OH | 148±5 | 20.7±0.2 | n.i. | 140±2 | 44±3 | 43.2±0.7 | n.i. | 982±51 |
H-Gln-Glu-OH | 359±10 | 24.7±0.2 | n.i. | 58±1 | 106±5 | 50.3±0.6 | n.i. | 475±17 |
H-Gln-Val-OH | 196±5 | 17.2±0.1 | n.i. | 88±2 | n.d. | n.d. | n.i. | n.d. |
H-Gln-Tyr-OH | 211±5 | 94±1 | n.i. | 446±6 | n.d. | n.d. | n.i. | n.d. |
H-Gln-Gln-Tyr-NH2 | 79±2 | 45.1±0.4 | n.i. | 524±8 | 103±4 | 53.6±0.7 | n.i. | 520±13 |
H-Gln-Gly-Pro-OH | 130±5 | 25.3±0.2 | n.i. | 195±7 | 333±15 | 41.7±0.5 | n.i. | 125±4 |
H-Gln-Tyr-Ala-OH | 101±4 | 125±1 | n.i. | 930±27 | 63±3 | 104.0±1.0 | n.i. | 1650±63 |
H-Gln-Phe-Ala-NH2 | 69±3 | 109±1 | n.i. | 1811±64 | 111±5 | 132.1±0.6 | n.i. | 1190±48 |
H-Gln-Trp-Ala-NH2 | 50±2 | 47.0±0.7 | n.i. | 940±24 | 78±5 | 151.8±2.6 | n.i. | 1946±91 |
H-Gln-Arg-Gly-Ile-NH2 | 143±4 | 33.5±0.4 | n.i. | 234±4 | 123±10 | 49.2±1.7 | n.i. | 400±19 |
H-Gln-Asn-Gly-Ile-NH2 | 172±5 | 56.6±0.5 | n.i. | 329±7 | 153±9 | 51.4±0.9 | n.i. | 336±14 |
H-Gln-Ser-Tyr-Phe-NH2 | 55±3 | 52.8±0.8 | n.i. | 960±38 | 135±6 | 64.9±1.0 | n.i. | 481±14 |
H-Gln-Arg-Tyr-Phe-NH2 | 55±2 | 29.6±0.3 | n.i. | 538±14 | 124±6 | 48.9±0.7 | n.i. | 394±13 |
H-Ghn-Pro-Tyr-Phe-NH2 | 1889±152 | 31.7±1.2 | n.i. | 17±1 | 149±14 | 18.8±0.6 | n.i. | 126±8 |
H-Gln-His-Tyr-Phe-NH2 | 68±3 | 55.4±0.7 | n.i. | 815±26 | 92±7 | 75.9±1.4 | n.i. | 825±48 |
H-Gln-Gln-Tyr-Phe-NH2 | 41±2 | 41.4±0.4 | n.i. | 1010±40 | 45±2 | 52.9±0.7 | n.i. | 1176±37 |
H-Gln-Glu-Tyr-Phe-NH2 | 47±4 | 46±1 | n.i. | 979±62 | 100±4 | 54.6±0.6 | n.i. | 546±16 |
H-Gln-Glu-Ala-Ala-NH2 | 77±4 | 46±1 | n.i. | 597±18 | 102±4 | 53.7±0.6 | n.i. | 526±15 |
H-Gln-Glu-Tyr-Ala-NH2 | 69±2 | 42.1±0.4 | n.i. | 610±12 | 113±5 | 44.7±0.5 | n.i. | 396±13 |
H-Gln-Glu-Ala-Phe-NH2 | 39±3 | 39±1 | n.i. | 1000±51 | 81±3 | 48.5±0.45 | n.i. | 599±17 |
H-Gln-Glu-Asp-Leu-NH2 | 55±2 | 45.8±0.5 | n.i. | 833±21 | 107±6 | 58.5±0.4 | n.i. | 547±27 |
H-Gln-Lys-Arg-Leu-NH2 | 54±3 | 33.4±0.5 | n.i. | 619±25 | 118±6 | 48.2±0.8 | n.i. | 408±14 |
底物 | 人QC | 木瓜QC | ||||
KM(μM) | Kcat(s-1) | kcat/KM(mM-1s-1) | KM(μM) | Kcat(s-1) | kcat/KM(mM-1s-1) | |
H-Gln-Ala-NH2 | 155±9 | 40.1±0.9 | 259±9 | 212±21 | 62.8±3.0 | 296±15 |
H-Gln-Ala-Ala-NH2 | 87±3 | 76.3±0.7 | 877±22 | 164±6 | 83.2±1.0 | 507±12 |
H-Gln-Ala-Ala-Ala-Ala-NH2 | 65±3 | 60.5±0.7 | 1174±43 | 197±8 | 74.6±1.0 | 379±10 |
H-Gln-Ala-Ala-Ser-Ala-Ala-NH2 | 79±6 | 55.3±1.6 | 700±33 | 216±6 | 78.5±1.0 | 363±5 |
底物 | 0.05M Tricine-NaOH,pH 8.0 | 0.05M Tricine-NaOH,pH 8.0,0.5M KCl | |||||||
木瓜QC | KM(mM) | Kcat(s-1) | kcat/KM(mM-1s-1) | Ki(mM) | KM(mM) | Kcat(s-1) | kcat/KM(mM-1s-1) | Ki(mM) | |
H-Gln-NH2 | 0.434±0.015 | 43.3±0.4 | 100±3 | n.i. | 0.446±0.010 | 45.2±0.3 | 101±2 | n.i. | |
H-Gln-βNA | 0.036±0.002 | 48.8±1.0 | 1356±50 | 1.14±0.05 | 0.032±0.002 | 47.2±0.8 | 1475±70 | 1.33±0.07 | |
H-Gln-Ala-OH | 0.137±0.007 | 69.7±0.9 | 509±19 | n.i. | 0.143±0.005 | 68.1±0.6 | 480±12 | n.i. | |
H-Gln-Glu-OH | 0.098±0.005 | 45.0±0.5 | 459±18 | n.i. | 0.094±0.003 | 44.4±0.3 | 472±12 | n.i. | |
H-Gln-Trp-Ala-NH2 | 0.079±0.005 | 138±3 | 1747±73 | n.i. | 0.072±0.004 | 133±3 | 1847±61 | n.i. | |
H-Gln-Arg-Gly-Ile-NH2 | 0.106±0.008 | 52.9±1.2 | 499±26 | n.i. | 0.065±0.005 | 48.4±1.0 | 745±42 | n.i. | |
H-Gln-Lys-Arg-Leu-NH2 | 0.102±0.007 | 50±1 | 493±22 | n.i. | 0.053±0.002 | 58.1±0.7 | 1096±28 | n.i. | |
H-Gln-Glu-Asp-Leu-NH2 | 0.109±0.005 | 52.4±0.7 | 481±16 | n.i. | 0.094±0.003 | 53.6±0.5 | 570±13 | n.i. |
人QC | 0.05M Tris-HCl,pH 8.0 | 0.05M Tris-HCl,pH 8.0,0.5M KCl | |||||||
H-Gln-NH2 | 0.442±0.030 | 12.8±0.3 | 29±1 | n.i. | 0.401±0.014 | 12.2±0.1 | 30±1 | n.i. | |
H-Gln-βNA | 0.076±0.004 | 21.7±0.5 | 285±8 | 1.39±0.08 | 0.063±0.003 | 20.0±0.4 | 318±9 | 0.97±0.04 | |
H-Gln-Ala-OH | 0.269±0.007 | 54.4±0.5 | 202±3 | n.i. | 0.357±0.012 | 47.6±0.6 | 133±3 | n.i. | |
H-Gln-Glu-OH | 0.373±0.015 | 21.4±0.3 | 57±2 | n.i. | 0.607±0.036 | 18.9±0.5 | 31±1 | n.i. | |
H-Gln-Trp-Ala-NH2 | 0.054±0.003 | 50.8±0.6 | 941±41 | n.i. | 0.056±0.002 | 50.0±0.4 | 893±25 | n.i. | |
H-Gln-Arg-Gly-Ile-NH2 | 0.166±0.013 | 31±1 | 187±9 | n.i. | 0.091±0.005 | 29.8±0.5 | 327±12 | n.i. | |
H-Gln-Lys-Arg-Leu-NH2 | 0.051±0.003 | 29.4±0.5 | 577±24 | n.i. | 0.034±0.001 | 31.6±0.3 | 929±19 | n.i. | |
H-Gln-Glu-Asp-Leu-NH2 | 0.060±0.002 | 46.6±0.5 | 777±18 | n.i. | 0.061±0.002 | 45.6±0.5 | 748±16 | n.i. |
肽 | KM(μM) | Kcat(s-1) | kcat/KM(mM-1s-1) |
[Gln3]Aβ3-11a[Gln3]Aβ3-11a[Gln3]Aβ3-21a[Gln3]Aβ3-40胰高血糖素(3-29) | 87±3#155±4162±1289±1019±1 | 55±1#41.4±0.462±340±210.0±0.2 | 632±10#267±4383±10449±28526±17 |
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US60/468,043 | 2003-05-05 | ||
US51203803P | 2003-10-15 | 2003-10-15 | |
US60/512,038 | 2003-10-15 | ||
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102112880A (zh) * | 2008-07-31 | 2011-06-29 | 前体生物药物股份公司 | 作为神经退行性疾病诊断/预后指示物的谷氨酰胺酰环化酶 |
CN102112880B (zh) * | 2008-07-31 | 2014-06-25 | 前体生物药物股份公司 | 作为神经退行性疾病诊断/预后指示物的谷氨酰胺酰环化酶 |
CN102612653A (zh) * | 2009-09-18 | 2012-07-25 | 前体生物药物股份公司 | 检测淀粉样蛋白β肽的新测定 |
CN103492582A (zh) * | 2011-02-17 | 2014-01-01 | 富士瑞生物诊断公司 | 用于测定HE4a的组合物和方法 |
CN103492582B (zh) * | 2011-02-17 | 2016-06-22 | 富士瑞生物诊断公司 | 用于测定HE4a的组合物和方法 |
CN105263927A (zh) * | 2013-03-15 | 2016-01-20 | 前体生物药物股份公司 | 新的抑制剂 |
CN105263927B (zh) * | 2013-03-15 | 2019-03-15 | 前体生物药物股份公司 | 谷氨酰胺酰环化酶抑制剂 |
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IL171339A (en) | 2011-11-30 |
ATE464889T1 (de) | 2010-05-15 |
HK1089964A1 (en) | 2006-12-15 |
EA200501700A1 (ru) | 2006-06-30 |
AU2004237408C1 (en) | 2010-04-01 |
IL206009A (en) | 2017-09-28 |
CA2524009C (en) | 2014-04-29 |
AU2004237408C9 (en) | 2010-04-15 |
AU2009227925A1 (en) | 2009-11-12 |
NZ543146A (en) | 2008-09-26 |
PL1620082T3 (pl) | 2010-10-29 |
JP5690463B2 (ja) | 2015-03-25 |
EA009291B1 (ru) | 2007-12-28 |
IL206009A0 (en) | 2010-11-30 |
EP1620082B9 (en) | 2010-08-25 |
EP1620082A2 (en) | 2006-02-01 |
AU2004237408A1 (en) | 2004-11-18 |
CN1784220B (zh) | 2011-08-03 |
BRPI0410078A (pt) | 2006-05-16 |
DK1620082T3 (da) | 2010-08-16 |
WO2004098625A2 (en) | 2004-11-18 |
MXPA05011861A (es) | 2006-02-17 |
EP1620082B1 (en) | 2010-04-21 |
AU2004237408B2 (en) | 2009-10-01 |
JP2006525278A (ja) | 2006-11-09 |
WO2004098625A3 (en) | 2005-06-23 |
AU2009227925B2 (en) | 2011-12-15 |
CA2524009A1 (en) | 2004-11-18 |
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