KR20200046488A - Active peptide of Octopus minor octopressin, and uses thereof - Google Patents
Active peptide of Octopus minor octopressin, and uses thereof Download PDFInfo
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- KR20200046488A KR20200046488A KR1020180127704A KR20180127704A KR20200046488A KR 20200046488 A KR20200046488 A KR 20200046488A KR 1020180127704 A KR1020180127704 A KR 1020180127704A KR 20180127704 A KR20180127704 A KR 20180127704A KR 20200046488 A KR20200046488 A KR 20200046488A
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- octopus
- peptide
- octopressin
- sequence
- behavior
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Abstract
Description
낙지 옥토프레신 활성 펩타이드, 및 이의 용도에 관한 것이다.Octopus octopus active peptide, and relates to the use thereof.
낙지(Octopus minor)는 분류학적으로 연체동물문 두족강 문어목 문어과(Animalia Cephalopoda Octopoda Octopodidae)에 속하며 한국, 중국, 일본 등 동북아시아 연안에 주로 서식한다. 낙지가 속한 두족강은 무척추동물 중 가장 뇌 구조가 발달되고, 지능이 높아 뇌신경과학 분야 연구 개발 가치가 크다. 특히, 어미 낙지는 산란 후 알이 부화하기까지의 약 3개월 동안 갯벌의 진흙 속에서 먹이를 먹지 않고 알을 끊임 없이 흔들어 돌보는 독특한 포란행동을 하는데, 비록 문어에 비해 훨씬 적은 숫자의 알을 낳지만 성체로 성장할 가능성이 매우 높다. The octopus (Octopus minor) is a taxonomically belonging to the Mollusk octopus (Animalia Cephalopoda Octopoda Octopodidae), which inhabit most coasts of Northeast Asia such as Korea, China, and Japan. The cephalopod, which octopus belongs to, has the most developed brain structure and high intelligence, so it has great value in research and development in the field of brain neuroscience. In particular, the mother octopus has a peculiar foraging behavior that does not feed on the eggs and constantly shakes them in the mud of the mudflats for about 3 months after hatching, after spawning, although it produces much fewer eggs than octopuses. It is very likely to grow into an adult.
한편, 옥시토신은 포유류에서 출산 시 자궁수축을 유도할 뿐만 아니라, 유방 근육을 수축시켜 모유의 사출을 일으키고 아기 울음소리에 민감하게 하며, 수면 부족 등 아기를 돌보는 데서 오는 스트레스를 완화시켜주는 모성 호르몬이다. 또한, 성별에 관계없이 뇌에서 작용하여 타인을 신뢰하고 애착관계를 형성하게 하는 사회성 조절 신경 펩타이드이기도 하다. 옥시토신은 현재 알약, 주사제, 스프레이 제제 등으로 의료 목적을 위해 널리 사용되고 있으며 인간을 포함한 모든 척추 동물에서 옥시토신과 유사한 유전자가 생식 기능을 돕는 것으로 알려져 있다. 무척추동물에는 옥시토신이 없지만, 몇몇 종에서 옥시토신과 유사한 호르몬이 알려져 있다. 예를 들어, 참문어에서 옥시토신 유사 호르몬인 옥토프레신은 참문어의 말초 조직을 수축시키고, 또 다른 옥시토신 유사 호르몬인 세팔로토신은 쭈꾸미의 삼투압 내성을 조절한다는 연구가 발표된 바 있다. 그러나, 산란 및 포란 등 모성행동이나 사회성과 관련된 기능 연구는 전무한 실정이며, 특히 인간의 옥시토신이나 참문어의 옥토프레신과 유사한 가진 유전자가 낙지에도 존재하는지 여부는 아직 밝혀진 바 없다. On the other hand, oxytocin is a maternal hormone that not only induces uterine contraction at birth in mammals, but also contracts the breast muscles to cause breast milk injection, makes babies sensitive to crying, and relieves stress from caring for babies such as lack of sleep. . It is also a socially-regulated neuropeptide that acts on the brain regardless of gender, trusting others and forming an attachment relationship. Oxytocin is currently widely used for medical purposes in pills, injections, sprays, and the like, and genes similar to oxytocin are known to aid reproductive function in all vertebrates, including humans. Invertebrates do not have oxytocin, but hormones similar to oxytocin are known in some species. For example, research has been published in octopus that octopresin, an oxytocin-like hormone, contracts the peripheral tissue of octopus, and another oxytocin-like hormone, cephalotocin, regulates the osmotic resistance of the cuckoo. However, there have been no studies on functional behaviors related to maternal behavior or sociality such as spawning and eggs, and it is not yet known whether a gene having similarity to human oxytocin or octopus octopresin exists in octopus.
일 양상은 서열번호 3의 아미노산 서열로 이루어진 낙지 옥토프레신 펩타이드를 제공하는 것이다. One aspect is to provide an octopus octopesin peptide consisting of the amino acid sequence of SEQ ID NO: 3.
다른 양상은 상기 펩타이드를 코딩하는 핵산을 제공하는 것이다.Another aspect is to provide a nucleic acid encoding the peptide.
다른 양상은 상기 핵산을 포함하는 재조합 벡터를 제공하는 것이다.Another aspect is to provide a recombinant vector comprising the nucleic acid.
다른 양상은 서열번호 3의 아미노산 서열로 이루어진 펩타이드를 유효성분으로 포함하는 조성물을 제공하는 것이다. Another aspect is to provide a composition comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 3 as an active ingredient.
다른 양상은 낙지에 필요한 유효량으로 상기 조성물을 투여하는 단계를 포함하는 낙지의 포란 행동을 촉진하는 방법을 제공하는 것이다. Another aspect is to provide a method of promoting the occlusion behavior of an octopus comprising administering the composition in an effective amount required for the octopus.
일 양상은 서열번호 3의 아미노산 서열로 이루어진 낙지 옥토프레신 펩타이드를 제공한다. One aspect provides an octopus octopesin peptide consisting of the amino acid sequence of SEQ ID NO: 3.
본 명세서에서 용어, "옥토프레신(Octopression, OTP)"은 낙지에서 분비되는 옥시토신 유사 호르몬으로서, 낙지의 유전체 분석 결과로부터 낙지에도 옥시토신과 유사한 옥토프레신 유전자가 존재함을 확인하였고, 상기 유전자가 성체 낙지에서 포란 행동과 유사 행동을 유도 및/또는 촉진시키는 것을 확인하였다. 따라서, 상기 펩타이드는 낙지의 포란 행동을 촉진할 뿐만 아니라, 성별과 관계없이 낙지의 사회성을 증진시켜 교미를 촉진함으로써 낙지 부분 양식에 적용하여 치어 부화 효율을 높일 수 있는 바, 낙지 자원의 증식에 이용될 수 있다. In this specification, the term, "octopressin (Octopression, OTP)" is an oxytocin-like hormone secreted from the octopus. From the results of the genomic analysis of the octopus, it was confirmed that an octopressin gene similar to oxytocin is also present in the octopus. It was confirmed that the adult octopus induces and / or promotes behaviour and similar behavior. Therefore, the peptide not only promotes occlusion behavior of octopus, but also promotes mating by promoting sociality of octopus irrespective of gender, so that it can be applied to the octopus subculture to increase the hatching efficiency, which is used for the growth of octopus resources. Can be.
일 구체예에서, 상기 펩타이드는 1번 아미노산과 6번 아미노산 사이에 이황화 결합이 형성된 것일 수 있다. 또한, 상기 펩타이드의 C-말단은 아민기(-NH2) 가 추가로 결합될 수 있다. 따라서, 활성을 가질 수 있다. In one embodiment, the peptide may be a disulfide bond formed between
본 명세서 내 용어, "펩타이드"는 아미노산이 펩타이드 결합에 의해 서로 결합되어 형성된 선형의 분자를 의미한다. 본 발명의 펩타이드는 당해 기술분야에 공지되어 있는 합성 방법, 예를 들어 고상 합성 기술(solid-phase synthesis technique)에 따라 제조될 수 있다. 또한 상기 펩타이드는 본 명세서에 기재된 서열번호 3의 아미노산 서열뿐만 아니라, 이의 생물학적 균등물도 포함할 수 있다. 예를 들면, 낙지의 포란 행동 및/또는 교미, 기타 생물학적 특성을 보다 더 개선시키기 위하여 아미노산 서열에 추가적인 변화를 줄 수 있다. 이러한 변형은 예를 들어, 아미노산 잔기의 결실, 삽입 및/또는 치환을 포함한다. 이러한 아미노산 변이는 아미노산 곁사슬 치환체의 상대적 유사성, 예컨대, 소수성, 친수성, 전하, 크기 등에 기초하여 이루어진다. 아미노산 곁사슬 치환체의 크기, 모양 및 종류에 대한 분석에 의하여, 아르기닌, 라이신과 히스티딘은 모두 양전하를 띤 잔기이고; 알라닌, 글라이신과 세린은 유사한 크기를 가지며; 페닐알라닌, 트립토판과 타이로신은 유사한 모양을 갖는다는 것을 알 수 있다. 따라서, 이러한 고려 사항에 기초하여, 아르기닌, 라이신과 히스티딘; 알라닌, 글라이신과 세린; 그리고 페닐알라닌, 트립토판과 타이로신은 생물학적으로 기능 균등물이라 할 수 있다.As used herein, the term "peptide" refers to a linear molecule formed by amino acids being bonded to each other by peptide bonds. The peptides of the present invention can be prepared according to synthetic methods known in the art, for example, solid-phase synthesis techniques. In addition, the peptide may include the amino acid sequence of SEQ ID NO: 3 described herein, as well as biological equivalents thereof. For example, additional changes can be made to the amino acid sequence to further improve octopus nesting behavior and / or mating, and other biological properties. Such modifications include, for example, deletion, insertion and / or substitution of amino acid residues. These amino acid variations are made based on the relative similarity of amino acid side chain substituents, such as hydrophobicity, hydrophilicity, charge, size, and the like. By analysis of the size, shape and type of amino acid side chain substituents, arginine, lysine and histidine are all positively charged residues; Alanine, glycine and serine have similar sizes; It can be seen that phenylalanine, tryptophan and tyrosine have similar shapes. Therefore, based on these considerations, arginine, lysine and histidine; Alanine, glycine and serine; And phenylalanine, tryptophan and tyrosine are biologically equivalent functions.
상기 변이를 도입하는 데 있어서, 아미노산의 소수성 인덱스(hydropathic index)가 고려될 수 있다. 각각의 아미노산은 소수성과 전하에 따라 소수성 인덱스가 부여되어 있다: 아이소루이신(+4.5); 발린(+4.2); 루이신(+3.8); 페닐알라닌(+2.8); 시스테인/시스타인(+2.5); 메티오닌(+1.9); 알라닌(+1.8); 글라이신(-0.4); 쓰레오닌(-0.7); 세린(-0.8); 트립토판(-0.9); 타이로신(-1.3); 프롤린(-1.6); 히스티딘(-3.2); 글루타메이트(-3.5); 글루타민(-3.5); 아스파르테이트(-3.5); 아스파라긴(-3.5); 라이신(-3.9); 및 아르기닌(-4.5). 단백질의 상호적인 생물학적 기능(interactive biological function)을 부여하는 데 있어서 소수성 아미노산 인덱스는 매우 중요하다. 유사한 소수성 인덱스를 가지는 아미노산으로 치환하여야 유사한 생물학적 활성을 보유할 수 있다는 것은 공지된 사실이다. 소수성 인덱스를 참조하여 변이를 도입시키는 경우, 바람직하게는 ± 2 이내, 보다 바람직하게는 ± 1 이내, 보다 더 바람직하게는 ± 0.5 이내의 소수성 인덱스 차이를 나타내는 아미노산 사이에 치환을 한다.In introducing the variation, the hydropathic index of amino acids can be considered. Each amino acid is assigned a hydrophobicity index according to hydrophobicity and charge: isoleucine (+4.5); Valine (+4.2); Leucine (+3.8); Phenylalanine (+2.8); Cysteine / cysteine (+2.5); Methionine (+1.9); Alanine (+1.8); Glycine (-0.4); Threonine (-0.7); Serine (-0.8); Tryptophan (-0.9); Tyrosine (-1.3); Proline (-1.6); Histidine (-3.2); Glutamate (-3.5); Glutamine (-3.5); Aspartate (-3.5); Asparagine (-3.5); Lysine (-3.9); And arginine (-4.5). The hydrophobic amino acid index is very important in conferring the protein's interactive biological function. It is well known that amino acids with similar hydrophobic indices can be replaced to retain similar biological activity. When introducing a variation with reference to the hydrophobic index, substitution between amino acids showing hydrophobic index difference is preferably within ± 2, more preferably within ± 1, even more preferably within ± 0.5.
한편, 유사한 친수성 값(hydrophilicity value)을 가지는 아미노산 사이의 치환이 균등한 생물학적 활성을 갖는 단백질을 초래한다는 것도 알려져 있다. 미국 특허 제4,554,101호에 개시된 바와 같이, 다음의 친수성 값이 각각의 아미노산 잔기에 부여되어 있다: 아르기닌(+3.0); 라이신(+3.0); 아스팔테이트(+3.0±1); 글루타메이트(+3.0±1); 세린(+0.3); 아스파라긴(+0.2); 글루타민(+0.2); 글라이신(0); 쓰레오닌(-0.4); 프롤린(-0.5±1); 알라닌(-0.5); 히스티딘(-0.5); 시스테인(-1.0); 메티오닌(-1.3); 발린(-1.5); 루이신(-1.8); 아이소루이신 (-1.8); 타이로신(-2.3); 페닐알라닌(-2.5); 트립토판(-3.4). 분자의 활성을 전체적으로 변경시키지 않는 단백질에서의 아미노산 교환은 당해 분야에 공지되어 있다(H. Neurath, R.L.Hill, The Proteins, Academic Press,New York, 1979). 가장 통상적으로 일어나는 교환은 아미노산 잔기 Ala/Ser, Val/Ile, Asp/Glu, Thr/Ser, Ala/Gly, Ala/Thr, Ser/Asn, Ala/Val, Ser/Gly, Thr/Phe, Ala/Pro, Lys/Arg, Asp/Asn, Leu/Ile, Leu/Val, Ala/Glu 및 Asp/Gly 간의 교환이다.On the other hand, it is also known that substitution between amino acids having a similar hydrophilicity value results in proteins having equivalent biological activity. As disclosed in US Pat. No. 4,554,101, the following hydrophilicity values are assigned to each amino acid residue: arginine (+3.0); Lysine (+3.0); Asphaltate (+ 3.0 ± 1); Glutamate (+ 3.0 ± 1); Serine (+0.3); Asparagine (+0.2); Glutamine (+0.2); Glycine (0); Threonine (-0.4); Proline (-0.5 ± 1); Alanine (-0.5); Histidine (-0.5); Cysteine (-1.0); Methionine (-1.3); Valine (-1.5); Leucine (-1.8); Isoleucine (-1.8); Tyrosine (-2.3); Phenylalanine (-2.5); Tryptophan (-3.4). Amino acid exchange in proteins that do not alter the overall activity of the molecule is known in the art (H. Neurath, R.L.Hill, The Proteins, Academic Press, New York, 1979). The most common exchanges are amino acid residues Ala / Ser, Val / Ile, Asp / Glu, Thr / Ser, Ala / Gly, Ala / Thr, Ser / Asn, Ala / Val, Ser / Gly, Thr / Phe, Ala / Pro, Lys / Arg, Asp / Asn, Leu / Ile, Leu / Val, Ala / Glu and Asp / Gly.
상술한 생물학적 균등 활성을 갖는 변이를 고려한다면, 본 발명의 펩타이드 또는 이를 코딩하는 핵산 분자는 서열번호에 기재된 서열과 실질적인 동일성(substantial identity)을 나타내는 서열도 포함하는 것으로 해석될 수 있다. 상기의 실질적인 동일성은, 상기한 본 발명의 서열과 임의의 다른 서열을 최대한 대응되도록 얼라인하고, 당업계에서 통상적으로 이용되는 알고리즘을 이용하여 얼라인된 서열을 분석한 경우에, 최소 61%의 상동성, 보다 바람직하게는 70%의 상동성, 보다 더 바람직하게는 80%의 상동성, 가장 바람직하게는 90%의 상동성을 나타내는 서열을 의미한다. 서열비교를 위한 얼라인먼트 방법은 당업계에 공지되어 있다. NCBI Basic Local Alignment Search Tool(BLAST)은 NBCI 등에서 접근 가능하며, 인터넷 상에서 blastp, blasm, blastx, tblastn 및 tblastx와 같은 서열 분석 프로그램과 연동되어 이용할 수 있다. BLAST는 https://blast.ncbi.nlm.nih.gov/Blast.cgi에서 접속 가능하다. 이 프로그램을 이용한 서열 상동성 비교 방법은 https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastp&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome에서 확인할 수 있다.Considering the above-described variation in biologically equivalent activity, the peptide of the present invention or a nucleic acid molecule encoding the same may be interpreted to include a sequence showing substantial identity with the sequence set forth in SEQ ID NO. The substantial identity above, when aligned with the above-described sequence of the present invention and any other sequence as much as possible, and analyzed by using an algorithm commonly used in the art, the aligned sequence is at least 61%. Refers to a sequence that exhibits homology, more preferably 70% homology, even more preferably 80% homology, and most preferably 90% homology. Alignment methods for sequence comparison are known in the art. NCBI Basic Local Alignment Search Tool (BLAST) can be accessed from NBCI, etc., and can be used in conjunction with sequence analysis programs such as blastp, blasm, blastx, tblastn and tblastx on the Internet. BLAST can be accessed at https://blast.ncbi.nlm.nih.gov/Blast.cgi. The sequence homology comparison method using this program can be found at https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastp&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome.
본 명세서 내 용어, "포란 행동"이란 부화하기 위하여 암컷 낙지가 알을 수시로 흔들어주는 행동을 의미한다. 낙지는 근연종인 문어나 주꾸미에 비하여 산란수가 적고 갯벌 속 깊은 은신처에서 어미 낙지의 독특한 포란 행동으로 부화한다(낙지(Octopus minor)의 배 발생. Embryogenesis in the Octopus minor. 김동수 식별저자, 김재만 식별저자. 발생과 생식 제10권 제2호, 2006.10, 135-140). 포란기의 암컷 낙지는 알을 낳아 자신이 분비한 진한 초록색 접착 물질을 이용하여 벽에 부착시키고, 팔(다리)와 빨판을 이용하여 수시로 알을 흔들어주는 독특한 행동을 한다. 또한, 치어가 부화하기까지 약 3개월 동안 상기 행동을 지속적으로 하며 그 동안 암컷 낙지는 먹이를 먹지 않고 알 곁을 지킨다. 즉, 상기 펩타이드는 낙지의 포란 행동을 촉진시킴으로써 낙지의 치어 부화 효율을 높일 수 있다. In this specification, the term "forge behavior" refers to the behavior of a female octopus shaking eggs from time to time to hatch. Octopus is enriched with a unique incubation behavior of the mother octopus in less sanransu tidal deep lair compared to closely related species, octopus or octopus (octopus (Octopus minor) of embryogenesis. Embryogenesis in the Octopus minor. Kim DS identify the author, Jae-man Kim identified the author. Development and Reproduction Vol. 10, No. 2, 2006.10, 135-140). The female octopus of the forage period lays eggs and attaches them to the wall using a dark green adhesive material secreted by them, and uses the arms (legs) and suckers to shake the eggs from time to time. In addition, the above behavior continues for about 3 months until the larvae hatch, while the female octopus keeps the eggs without feeding. That is, the peptide can increase the efficiency of the octopus pom-pom hatching by promoting the octopus nesting behavior.
본 명세서에서 용어, "사회적 행동"이란 성별과 관계없이 낙지의 사회성을 증진시켜 교미(copulation)를 촉진하기 위한 행동을 의미한다. 즉, 산란기에 진입한 낙지는 여러 개의 팔(다리)을 구부렸다 펴는 반복적인 행동을 나타내고, 다른 낙지에 접근하거나 팔(다리)를 뻗어 건드리고 닦아주는 듯한 행동을 나타내며 암 수컷이 함께 같이 붙어있으면서 팔(다리) 전체를 꼬면서 교접 행동과 같은 사회적 행동을 한다. As used herein, the term "social action" refers to an action to promote copulation by promoting octopus sociality regardless of gender. In other words, the octopus that entered the spawning period exhibits repetitive actions of bending and stretching several arms (legs), approaching another octopus, or stretching and stretching the arms (legs), and acts like wiping and wiping arms. Legs) social activities, such as entanglement, while twisting the whole.
무척추동물인 지렁이에서는 옥시토신과 유사한 아네토신(annetocin)이 분비되는데, 아네토신을 지렁이에 주사하면 산란할 때 보이는 특징적인 행동을 유도할 뿐만 아니라, 알을 낳는 개체를 확인할 수 있다(J Exp Zool. 1996 Oct 1;276(2):151-6. Annetocin, an annelid oxytocin-related peptide, induces egg-laying behavior in the earthworm, Eisenia foetida). 즉, 척추동물에서 옥시토신은 출산, 수유 및 자녀 양육에 관여하고 무척추동물인 지렁이에서는 옥시토신 유사 물질이 교미와 산란을 유도할 수 있다. 따라서, 상기 조성물은 낙지의 포란 행동을 촉진시킴으로써 낙지의 치어 부화 효율을 높일 수 있는바, 낙지의 생산량을 증대시킬 수 있다.An invertebrate, an earthworm, releases antocin similar to oxytocin, which injects anetocin into the earthworm, which not only induces the characteristic behavior seen during spawning, but also identifies the egg-laying individual (J Exp Zool. 1996 Oct 1; 276 (2): 151-6.Annetocin, an annelid oxytocin-related peptide, induces egg-laying behavior in the earthworm, Eisenia foetida ). In other words, in vertebrates, oxytocin is involved in childbirth, lactation and child rearing, and invertebrates, earthworms, oxytocin-like substances can induce mating and spawning. Therefore, the composition can increase the production efficiency of the octopus by increasing the efficiency of the incubation of the octopus by promoting the occlusion behavior of the octopus.
다른 양상은 상기 펩타이드를 코딩하는 핵산을 제공한다. 상기 펩타이드의 구체적인 내용은 전술한 바와 같다. 일 구체예에서, 상기 핵산은 서열번호 1로 표시되는 염기서열을 포함할 수 있다. 또한 상기 염기서열은 서열번호 2의 아미노산 서열로 코딩되는 오픈리딩 프레임(open reading frame)을 포함할 수 있다. Another aspect provides a nucleic acid encoding the peptide. The details of the peptide are as described above. In one embodiment, the nucleic acid may include a nucleotide sequence represented by SEQ ID NO: 1. Further, the base sequence may include an open reading frame encoded with the amino acid sequence of SEQ ID NO: 2.
본 명세서 내 용어, "핵산(nucleic acid)"은 DNA(gDNA 및 cDNA) 및 RNA 분자를 포괄적으로 포함하는 의미를 가지며, 핵산에서 기본 구성단위인 뉴클레오타이드는 자연의 뉴클레오타이드 뿐만아니라, 당 또는 염기 부위가 변형된 유사체(analogue)도 포함한다. 본 발명의 중쇄 및 경쇄 가변영역을 코딩하는 핵산의 서열은 변형될 수 있다. 상기 변형은 뉴클레오타이드의 추가, 결실, 또는 비보존적 치환 또는 보존적 치환을 포함한다.As used herein, the term “nucleic acid” has the meaning of comprehensively including DNA (gDNA and cDNA) and RNA molecules. Nucleotides, which are basic structural units in nucleic acids, are not only natural nucleotides, but also sugar or base sites. Also includes modified analogues. The sequences of nucleic acids encoding the heavy and light chain variable regions of the invention can be modified. Such modifications include addition, deletion, or non-conservative substitutions or conservative substitutions of nucleotides.
본 발명의 핵산은 상기 뉴클레오타이드 서열에 대하여 실질적인 동일성을 나타내는 뉴클레오타이드 서열도 포함하는 것으로 해석된다. 실질적인 동일성은 본 발명의 뉴클레오타이드 서열과 임의의 다른 서열을 최대한 대응되도록 얼라인하고, 당업계에서 통상적으로 이용되는 알고리즘을 이용하여 얼라인 된 서열을 분석한 경우에, 최소 80%의 상동성, 보다 바람직하게는 최소 90%의 상동성, 가장 바람직하게는 최소 95%의 상동성을 나타내는 뉴클레오타이드 서열을 의미한다.The nucleic acid of the present invention is also interpreted to include a nucleotide sequence showing substantial identity to the nucleotide sequence. Substantial identity aligns the nucleotide sequence of the present invention with any other sequence for maximum correspondence, and when the aligned sequence is analyzed using an algorithm commonly used in the art, at least 80% homology, more Preferably, it means a nucleotide sequence exhibiting at least 90% homology, most preferably at least 95% homology.
상기 펩타이드를 암호화하는 DNA는 통상적인 과정을 사용하여 용이하게 분리 또는 합성한다. 많은 벡터가 입수 가능하다. 벡터 성분에는 일반적으로, 다음 중의 하나 이상이 포함되지만, 그에 제한되지 않는다: 신호 서열, 복제 기점, 하나 이상의 마커 유 전자, 증강인자 요소, 프로모터, 및 전사 종결 서열.The DNA encoding the peptide is easily separated or synthesized using conventional procedures. Many vectors are available. Vector components generally include, but are not limited to, one or more of the following: signal sequences, origins of replication, one or more marker genes, enhancer elements, promoters, and transcription termination sequences.
다른 양상은 상기 핵산을 포함하는 재조합 벡터를 제공한다. 상기 핵산의 구체적인 내용은 전술한 바와 같다. 일 구체예에서, 상기 재조합 벡터는 서열번호 9 및 10의 프라이머를 포함할 수 있다. Another aspect provides a recombinant vector comprising the nucleic acid. The details of the nucleic acid are as described above. In one embodiment, the recombinant vector may include primers of SEQ ID NOs: 9 and 10.
본 명세서 내 용어, "벡터"는 숙주세포에서 목적 유전자를 발현시키기 위한 수단으로 플라스미드 벡터; 코즈미드 벡터; 박테리오파지 벡터, 아데노바이러스 벡터, 레트로바이러스 벡터 및 아데노-연관 바이러스벡터 같은 바이러스벡터 등을 포함한다. 상기 벡터에서 항체를 코딩하는 핵산은 프로모터와 작동적으로 연결되어 있다.As used herein, the term "vector" means a plasmid vector as a means for expressing a target gene in a host cell; Cosmid vectors; Viral vectors such as bacteriophage vectors, adenovirus vectors, retroviral vectors, and adeno-associated virus vectors. The nucleic acid encoding the antibody in the vector is operably linked to a promoter.
"작동적으로 연결"은 핵산 발현조절서열(예: 프로모터, 시그널 서열, 또는 전사조절인자 결합 위치의 어레이)과 다른 핵산 서열사이의 기능적인 결합을 의미하며, 이에 의해 상기 조절서열은 상기 다른 핵산 서열의 전사 및/또는 해독을 조절하게 된다."Operatively linked" refers to a functional binding between a nucleic acid expression control sequence (eg, an array of promoters, signal sequences, or transcription regulator binding sites) and another nucleic acid sequence, whereby the control sequence is the other nucleic acid. It controls the transcription and / or translation of sequences.
원핵세포를 숙주로 하는 경우에는, 전사를 진행시킬 수 있는 강력한 프로모터(예컨대, tac 프로모터, lac 프로모터, lacUV5 프로모터, lpp 프로모터, pL
본 발명은 또 다른 관점에서, 상기 언급된 벡터로 형질전환된 세포를 제공한다. 본 발명의 펩타이드를 생성시키기 위해 사용된 세포는 원핵생물, 효모 또는 고등 진핵생물 세포일 수 있으며, 이에 제한되는 것은 아니다. 에스케리치아 콜라이(Escherichia coli), 바실러스 서브틸리스 및 바실러스 츄린겐시스와 같은 바실러스 속 균주, 스트렙토마이세스(Streptomyces), 슈도모나스(Pseudomonas)(예를 들면, 슈도모나스 푸티다(Pseudomonas putida)), 프로테우스 미라빌리스(Proteus mirabilis) 및 스타필로코쿠스(Staphylococcus)(예를 들면, 스타필로코쿠스 카르노수스(Staphylocus carnosus))와 같은 원핵 숙주세포를 이용할 수 있다. 다만, 동물 세포에 대한 관심이 가장 크며, 유용한 숙주 세포주의 예는 COS-7, BHK, CHO, CHOK1, DXB-11, DG-44, CHO/-DHFR, CV1, COS-7, HEK293, BHK, TM4, VERO, HELA, MDCK, BRL 3A, W138, Hep G2, SK-Hep, MMT, TRI, MRC 5, FS4, 3T3, RIN, A549, PC12, K562, PER.C6, SP2/0, NS-0, U20S, 또는 HT1080일 수 있다. In another aspect, the present invention provides cells transformed with the above-mentioned vector. The cells used to generate the peptides of the present invention may be prokaryotic, yeast or higher eukaryotic cells, but are not limited thereto. Bacillus strains such as Escherichia coli, Bacillus subtilis and Bacillus thuringiensis, Streptomyces, Pseudomonas (e.g., Pseudomonas putida), Proteus Prokaryotic host cells such as Proteus mirabilis and Staphylococcus (e.g. Staphylococcus carnosus) can be used. However, the interest in animal cells is the most, and examples of useful host cell lines are COS-7, BHK, CHO, CHOK1, DXB-11, DG-44, CHO / -DHFR, CV1, COS-7, HEK293, BHK, TM4, VERO, HELA, MDCK, BRL 3A, W138, Hep G2, SK-Hep, MMT, TRI,
다른 양상은 서열번호 3의 아미노산 서열로 이루어진 펩타이드를 유효성분으로 포함하는 조성물을 제공한다. 상기 펩타이드의 구체적인 내용은 전술한 바와 같다. 또한, 다른 양상은 낙지에 필요한 유효량으로 상기 조성물을 투여하는 단계를 포함하는 낙지의 포란 행동을 촉진하는 방법을 제공한다. 상기 조성물은 해당 기술분야에 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법으로 동물용 주사제, 산제, 액제 또는 과립제, 정제로 제형화될 수 있다. 예를 들어 동물용 주사제 및 경구용 액제의 경우에는 약제학적으로 허용 가능한 담체로서 증류수, 에틸올레티트, 에탄올, 프로필렌글리콜, 글리세린 등을 사용할 수 있다. 또한, 항산화제로서 아스코르빈산, 아황산수소나트륨, 피로아황산나트륨, 토코페롤 등을 사용할 수 있으며, 보존제로서 질산페닐수은, 티메로살, 염화벤잘코늄, 페놀, 크레솔, 파라옥시메틸벤조에이트, 벤질알코올 등을 이용하여 제형화시킬 수 있다. 또한, 동물용 산제 및 과립제의 경우에는 비타민류, 글루코스, 락토스 등의 당류, 전분 또는 각종 분말 및 액상효소를 적량 사용하여 제형화할 수 있다. 또한, 상기 조성물의 투여는 주사제로서는 머리 또는 몸통에 투여되고, 액제의 경우에는 직접 경구 또는 음용수에 혼합하여 투여할 수 있으며, 산제 및 과립제는 음용수 및 사료에 혼합하여 투여할 수 있다. Another aspect provides a composition comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 3 as an active ingredient. The details of the peptide are as described above. In addition, another aspect provides a method for promoting occlusion behavior of an octopus comprising administering the composition in an effective amount required for the octopus. The composition may be formulated as an injection, powder, liquid or granule for animals, tablets in a manner that can be easily carried out by those skilled in the art. For example, in the case of animal injections and oral liquids, distilled water, ethyl oleate, ethanol, propylene glycol, glycerin, and the like can be used as pharmaceutically acceptable carriers. In addition, as an antioxidant, ascorbic acid, sodium hydrogen sulfite, sodium pyrosulfite, tocopherol, and the like can be used. As a preservative, phenyl mercury nitrate, thimerosal, benzalkonium chloride, phenol, cresol, paraoxymethylbenzoate, benzyl It can be formulated using alcohol or the like. In addition, in the case of animal powders and granules, vitamins, glucose, lactose, and other sugars, starches, or various powders and liquid enzymes can be used to formulate. In addition, administration of the composition may be administered to the head or body as an injection, and in the case of a liquid, it may be administered directly by mixing with oral or drinking water, and powder and granule may be mixed with drinking water and feed.
일 구체예에서, 상기 조성물은 낙지의 포란 행동 및/또는 교미를 촉진하기 위하여 서열번호 3의 아미노산 서열로 이루어진 펩타이드를 유효성분으로 포함할 수 있다. 상기 조성물은 당업계에 공지된 다양한 제조방법에 따라 적절한 유효 농도 범위에서 상기 펩타이드를 첨가하여 제조가능하며, 상기 펩타이드는 전체 조성물 중 0.01 내지 100중량%, 0.01 내지 90 중량%, 0.01 내지 80 중량%, 0.01 내지 70 중량%, 0.01 내지 60 중량% 또는 0.01 내지 50 중량%의 비율로 포함할 수 있다. 또한, 1 내지 3회 반복적으로 투여할 수 있다. 구체적으로, 1 내지 3회, 1 내지 2회 또는 2 내지 3회 투여할 수 있다. 이때, 투여 횟수가 상기 범위를 초과하는 경우, 낙지가 죽는 문제점이 있다. 상기 조성물을 투여한 낙지는 5 내지 30분 동안 포란 행동 및/또는 교미 촉진 행동을 지속할 수 있다. 구체적으로, 5 내지 30분, 5 내지 25분, 5 내지 20분, 5 내지 15분, 5 내지 10분, 10 내지 20분, 10 내지 15분 동안 지속할 수 있다. 또한, 투여 횟수에 따라 낙지의 포란 행동 및/또는 교미 촉진 행동의 지속 시간이 증가할 수 있다. In one embodiment, the composition may include a peptide consisting of the amino acid sequence of SEQ ID NO: 3 as an active ingredient in order to promote occlusion behavior and / or mating. The composition can be prepared by adding the peptide in an appropriate effective concentration range according to various manufacturing methods known in the art, the peptide is 0.01 to 100% by weight, 0.01 to 90% by weight, 0.01 to 80% by weight of the total composition , 0.01 to 70% by weight, 0.01 to 60% by weight or 0.01 to 50% by weight. Moreover, it can be administered repeatedly 1-3 times. Specifically, it may be administered 1 to 3 times, 1 to 2 times, or 2 to 3 times. At this time, when the number of administrations exceeds the above range, there is a problem that the octopus dies. Octopus administered with the composition may continue to be incubating and / or mating promoting for 5 to 30 minutes. Specifically, it may last for 5 to 30 minutes, 5 to 25 minutes, 5 to 20 minutes, 5 to 15 minutes, 5 to 10 minutes, 10 to 20 minutes, and 10 to 15 minutes. In addition, the duration of occlusion behavior and / or mating-promoting behavior of octopus may increase depending on the number of administrations.
일 양상에 따른 옥토프레신 전구체 단백질 및 활성 펩타이드는 낙지에서 분비되는 옥시토신 유사 호르몬으로 어미 낙지의 포란 행동을 촉진하고 성별과 관계없이 낙지의 사회성을 증진시켜 교미를 촉진함으로써 낙지 부분 양식에 적용하여 치어 부화 효율을 높일 수 있는 바, 낙지 자원의 증식에 이용될 수 있다.Octopressin precursor protein and active peptide according to one aspect are oxytocin-like hormones secreted from the octopus to promote the occlusion behavior of the mother octopus and promote the maturity of the octopus irrespective of sex to promote mating, thereby applying to the octopus partial form. As the hatching efficiency can be increased, it can be used for the propagation of octopus resources.
도 1은 어미 낙지의 포란 행동을 관찰한 사진이다.
도 2는 낙지 유전체에서 옥토프레신 유전자의 구조도를 나타낸 모식도이다(인트론 크기 1/100 축소).
도 3은 낙지의 뇌에서 옥토프레신 일부 유전자를 증폭한 결과를 나타낸다.
도 4는 낙지의 뇌에서 옥토프레신(코딩 염기서열 포함) 전체 유전자를 증폭한 결과를 나타낸다.
도 5는 클로닝한 벡터에서 옥토프레신 유전자에 해당하는 부분을 증폭한 결과를 나타낸다.
도 6은 MEGA6 프로그램을 이용하여 옥토프레신 염기서열을 정렬한 결과를 나타낸다.
도 7은 MEGA6 프로그램을 이용하여 옥토프레신 아미노산 서열을 정렬한 결과를 나타낸다.
도 8a는 옥토프레신 아미노산 서열 및 변형을 만족하는 합성 펩타이드 주사 후 낙지의 행동 변화를 나타낸 사진이다.
도 8b는 옥토프레신을 주사한 낙지가 포란 행동 유사 행동을 보이는 것을 나타낸 사진이다. 1 is a picture of observing the nest behavior of the mother octopus.
Figure 2 is a schematic diagram showing the structure of the octopressin gene in the octopus genome (
3 shows the results of amplifying some genes of octopressin in the octopus brain.
Figure 4 shows the results of amplifying the entire gene octopresin (including coding base sequence) in the octopus brain.
5 shows a result of amplifying a portion corresponding to the octopressin gene in the cloned vector.
Figure 6 shows the results of aligning the octopressin base sequence using the MEGA6 program.
7 shows the results of aligning the octopressin amino acid sequence using the MEGA6 program.
8A is a photograph showing the behavioral change of octopus after injection of a synthetic peptide that satisfies the octopressin amino acid sequence and modification.
8B is a photograph showing that octopus injected with octopressin exhibits a behavior similar to that of a porosity.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 하기 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred embodiments are provided to help understanding of the present invention. However, the following examples are only provided to more easily understand the present invention, and the contents of the present invention are not limited by the following examples.
[실시예][Example]
실시예 1. 어미 낙지 포란 행동 분석 및 조절 유전자 발굴Example 1. Analysis of the mother octopus nest behavior and discovery of regulatory genes
1-1. 어미 낙지 포란 행동 분석1-1. Mother octopus behavior analysis
포란 행동을 관찰하기 위해 전남해양수산과학원 서부지부 자원조성과와 협업을 통해 어미 낙지를 확보하였다. 전라남도 신안군 주변 바다에서 2017년 4~6월에 채집한 성숙 개체들(무게 180~330 g)을 구입하여, 양파망에 암컷과 수컷을 한 마리씩 넣고 자원조성과 내의 자연해수 양식장에 1주일간 순치하여 교미를 유도한 후, 암컷 낙지만 남겨 산란을 유도하였다. 산란 전까지 바지락을 먹이로 공급하며(1회/1주), 산란 후에는 먹이공급을 중단하고, 1개월 이상 순치 후 자원관내 인공해수 사육시설(18℃)로 이동하여 유지 및 관찰하였다.In order to observe the behavior of the nest, the mother octopus was secured through cooperation with the resource development of the western branch of the Jeonnam Marine and Fisheries Science Academy. Purchasing mature individuals (weight 180-330 g) collected in April-June 2017 from the sea around Sinan-gun, Jeollanam-do, putting one female and one male into the onion net, and then feeding them to the natural sea farm within 1 week. After inducing mating, only female octopus was left to induce spawning. Feed the clams before spawning (once per week), stop feeding after spawning, move to an artificial seawater breeding facility (18 ℃) in the resource building after a month or more of patrol to maintain and observe it.
도 1은 어미 낙지의 포란 행동을 관찰한 사진이다. 도 1에 나타난 바와 같이, 어미 낙지는 알을 낳아 자신이 분비한 진한 초록색 접착물질을 이용하여 벽에 부착시키고, 팔(다리)과 빨판을 이용해 수시로 알을 흔들어 주는 독특한 포란 행동을 보였다. 이 행동은 치어가 부화하기까지 약 3달 동안 계속되었으며 그 동안 어미 낙지는 먹이를 먹지 않고 알 곁을 지키는 것을 관찰할 수 있었다. 자연 상태에서는 갯벌 진흙 속에 굴을 파서 산란하고 동일한 포란행동을 수행하는 것으로 알려져 있으며, 어미 낙지의 이러한 행동은 알의 표면을 깨끗하게 닦아주고 주변의 해수를 순환시켜주는 효과가 있다. 1 is a picture of observing the nest behavior of the mother octopus. As shown in Figure 1, the mother octopus lays eggs and attaches them to the wall using a dark green adhesive substance secreted by them, and exhibits a unique enveloping behavior that frequently shakes eggs using arms (legs) and suckers. This action lasted for about three months before the larvae hatched, during which time the mother octopus was observed feeding on the eggs without feeding. In the natural state, it is known to dig and lay oysters in mud flat mud and perform the same nesting behavior. This behavior of the mother octopus has the effect of cleaning the surface of eggs and circulating the surrounding seawater.
1-2. 조절 유전자 발굴1-2. Discovering regulatory genes
낙지의 포란 행동과 관련된 유전자를 확인하기 위하여 전장유전체 분석을 실시하였다. 구체적으로, 낙지의 DNA를 추출한 후 차세대염기서열분석기법(NGS)과 생물정보학적 방법을 통해 전장유전체 분석을 실시하여 많은 숫자의 유전자 데이터를 확보하였다. 이후, 상기 데이터를 마이닝(mining)하여 옥시토신이나 문어의 옥토프레신과 유사한 유전자로 주석(annotation)되는 유전자가 존재하는 것을 확인하였다. 상기 결과로부터 약 147kb 길이의 옥시토신 유사 유전자 정보를 확보하였으며, 이를 낙지의 옥토프레신으로 명명하였다(표 1).Full length genome analysis was performed to identify genes involved in octopus nesting behavior. Specifically, after extracting the DNA of the octopus, full-length genome analysis was performed through next-generation base sequencing techniques (NGS) and bioinformatics methods to secure a large number of genetic data. Subsequently, it was confirmed that a gene annotated with a gene similar to oxytocin or octopusin of octopus exists by mining the data. From the above results, oxytocin-like gene information of about 147 kb in length was obtained, which was named octopus of octopus (Table 1).
도 2는 낙지 옥토프레신 유전자 구조를 분석한 그림이다. 도 2에 나타난 바와 같이, 옥토프레신 유전자의 유전체상 전장염기서열 정보로부터 옥시토신 유전자와 유사한 구조를 확인할 수 있었다. Figure 2 is a picture of the octopus octopin gene structure analysis. As shown in FIG. 2, a structure similar to the oxytocin gene could be confirmed from the full-length sequence information on the genome of the octopressin gene.
또한, 전사체 분석 결과에서, 낙지의 옥토프레신 mRNA는 발생 초기에는 발현하지 않지만 발생과정이 진행되면서 점점 발현량이 증가하는 것을 확인할 수 있었다. 구체적으로, 성체에서는 뇌와 장에서 많이 발현되고 정포, 위 간, 입에서는 적게 발현되었으며 팔(다리), 아가미, 눈, 심장, 신장, 피부, 난소, 호흡관, 독샘 등에서는 발현되지 않는 것을 확인할 수 있었다. In addition, in the results of transcriptome analysis, it was confirmed that octopusin mRNA of octopus was not expressed in the early stage of development, but the expression level increased gradually as the development process progressed. Specifically, it was confirmed that it was expressed a lot in the brain and intestine in adults, less in the sperm, stomach liver, and mouth, and was not expressed in the arms (legs), gills, eyes, heart, kidneys, skin, ovaries, respiratory tract, and poison glands. Could.
상기와 같은 결과를 통해 낙지의 옥토프레신은 인간의 옥시토신과 유사할 가능성이 있음을 예측할 수 있었다. 즉, 어미 낙지의 경우 옥토프레신의 발현량이 크게 증가하여 포란 행동을 유도하고 포란 기간 동안 식욕을 억제시키는 것으로 예상되는 바, 낙지 부분 양식에 적용하여 치어 부화 효율을 높일 수 있다. Through the above results, it was possible to predict that octopus of octopus may be similar to human oxytocin. That is, in the case of the mother octopus, it is expected that the expression level of octopressin is significantly increased to induce the behavior of incubation and to suppress the appetite during the period of incubation.
실시예 2. 조절 유전자 분석Example 2. Regulatory gene analysis
2-1. 옥토프레신 유전자의 코딩 염기서열 분석2-1. Analysis of coding sequence of octopressin gene
상기 실시예 1에서 낙지의 유전체 분석을 통해 예측한 옥토프레신 유전자의 코딩 서열을 분석하였다. 구체적으로, 유전체 분석 결과로 얻은 코딩 염기서열(CDS) 부위를 NCBI의 ORF finder 프로그램(https://www.ncbi.nlm.nih.gov/orffinder/)에 입력하여 가능한 ORF(open reading frame)의 목록을 얻었다. 그 중 길이가 가장 긴 ORF의 아미노산 서열을 NCBI의 protein blast(blastX) 프로그램으로 분석한 결과, 다른 생물 종의 옥시토신 유사 유전자들의 아미노산 서열과 유사한 부분이 있음을 확인하여 옥토프레신 전구체 단백질임을 알 수 있었다. In Example 1, the coding sequence of the octopressin gene predicted through octopus genomic analysis was analyzed. Specifically, the coding sequence (CDS) region obtained as a result of the genomic analysis can be input into NCBI's ORF finder program (https://www.ncbi.nlm.nih.gov/orffinder/) to obtain an open reading frame (ORF). Got a list. As a result of analyzing the amino acid sequence of the longest ORF with NCBI's protein blast (blastX) program, it can be seen that it is an octopressin precursor protein by confirming that there is a similar portion to the amino acid sequence of oxytocin-like genes of other biological species. there was.
2-2. 옥토프레신 활성 아미노산 서열 분석2-2. Octopresin active amino acid sequence analysis
상기 실시예 2-1에서 분석한 활성 펩타이드의 아미노산 서열을 분석하였으며, 상기 아미노산 서열은 하기와 같다; The amino acid sequence of the active peptide analyzed in Example 2-1 was analyzed, and the amino acid sequence is as follows;
N'- CFWTNCPVG-NH2 -C'. N'-CFWTNCPVG-NH 2 -C '.
구체적으로, 인간 옥시토신 전구체 단백질의 아미노산 서열과 비교하여 유사한 부위를 찾아서 예측하였다. 그 결과, 활성 펩타이드로 예상되는 아미노산 서열의 앞에는 시그널 펩타이드가, 뒤에는 절단 부위(cleavage site)와 뉴로피신(neurophysin) 유사 부위가 존재하여, 인간의 옥시토신 전구체 및 참문어의 옥토프레신과 비슷한 구조를 보였다. 낙지의 옥토프레신 활성 펩타이드의 아미노산 서열은 9개의 아미노산으로 구성되어 있고, 2개의 시스테인 위치도 각각 동일하였으며, 글리신으로 종결된다는 점에서, 다른 옥시토신 계열 펩타이드와 유사한 것을 확인할 수 있었다. 즉, 낙지의 옥토프레신은 1번 아미노산(시스테인)과 6번 아미노산(시스테인) 사이에 이황화 결합(disulfide bond) 결합이 형성되고, 9번 아미노산(글리신)의 C 말단(C-terminal) 부위에 NH2가 추가되는 아미드화(amidation)가 일어나서 활성 펩타이드로 작용할 수 있다. 또한, 낙지의 옥토프레신 활성 펩타이드의 아미노산 서열은 참문어의 옥토프레신 아미노산 서열과는 다른 신규한 옥토프레신인 것을 확인할 수 있었다(표 2). Specifically, a similar site was predicted by comparing the amino acid sequence of the human oxytocin precursor protein. As a result, the signal peptide was in front of the amino acid sequence expected to be the active peptide, followed by the cleavage site and the neurophysin-like site, showing a structure similar to that of human oxytocin precursors and octopus octopressin. . The amino acid sequence of the octopusin active peptide of octopus is composed of 9 amino acids, the two cysteine positions are the same, respectively, and it was confirmed that it is similar to other oxytocin-based peptides in that it is terminated with glycine. That is, octopusin of octopus has a disulfide bond bond formed between amino acid 1 (cysteine) and amino acid 6 (cysteine) and NH at the C-terminal site of amino acid 9 (glycine). Amidation, in which 2 is added, occurs and can act as an active peptide. In addition, it was confirmed that the amino acid sequence of the octopusin active peptide of octopus is a novel octopressin different from the octopusin amino acid sequence of octopus (Table 2).
실시예Example 3. 낙지 3. Octopus 옥토프레신Octopresin 유전자의 cDNA 합성 및 Gene cDNA synthesis and 옥토프레신의Octopressin 발현 여부 확인 Confirmation of expression
3-1. 낙지 옥토프레신 유전자의 cDNA 합성3-1. CDNA synthesis of octopus octopin gene
2017년 봄에 한국 남서해안에서 수산물 유통을 목적으로 어획한 암컷 낙지(평균 무게 183.5g) 8마리를 구매하여 3개월 이상 사육수조에 순치시켰다. 이후, 상기 낙지의 뇌를 분리하여 호일에 싼 후 -70℃에서 급속 냉동하였다. 냉동시킨 뇌를 망치로 분쇄하여 가루로 만든 후, Isoplus(Takara) 용액 3㎖에 넣고 용해시킨 다음 혼합 용액 1㎖로부터 RNA를 추출하였다. 이후, SuperScriptTM IV First strand synthesis system(Invitrogen)을 사용하여 RNA 1㎍으로부터 cDNA를 합성하고, 상기 합성한 cDNA로부터 옥토프레신 유전자를 증폭하기 위해 프라이머를 디자인하였다(표 3).In the spring of 2017, eight female octopus (average weight 183.5g) caught for the purpose of distributing aquatic products on the southwest coast of Korea were purchased and placed in breeding tanks for more than three months. Thereafter, the octopus brain was separated, wrapped in foil, and rapidly frozen at -70 ° C. After crushing the frozen brain with a hammer, it was dissolved in 3 ml of an Isoplus (Takara) solution, and then RNA was extracted from 1 ml of the mixed solution. Then, a superscript TM IV First strand synthesis system (Invitrogen) was used to synthesize cDNA from 1 μg of RNA, and primers were designed to amplify the octopressin gene from the synthesized cDNA (Table 3).
3-2. 옥토프레신 발현 여부 확인3-2. Confirmation of expression of octopressin
낙지의 뇌에서 옥토프레신 유전자가 발현하는지 여부를 확인하기 위하여 상기 실시예 3-1에서 디자인한 cDNA의 프라이머(서열번호 9~10)를 사용하여 옥토프레신 유전자의 일부에 대해 RT-PCR을 수행(95℃, 5분 → (94℃, 30초 → 67℃, 30 초 → 72℃, 30 초) x 35 사이클 → 72℃, 10 분 → 10℃ ∞)하였다. 이후, 증폭된 PCR 산물을 1.2% 아가로즈 겔에 전기영동하여 DNA 밴드를 확인하였다. RT-PCR was performed on a portion of the octopressin gene using the cDNA primer (SEQ ID NOs: 9 to 10) designed in Example 3-1 to confirm whether the octopusin gene was expressed in the octopus brain. It was performed (95 ℃, 5 minutes → (94 ℃, 30 seconds → 67 ℃, 30 seconds → 72 ℃, 30 seconds) x 35 cycles → 72 ℃, 10 minutes → 10 ℃ ∞). Thereafter, the amplified PCR product was electrophoresed on a 1.2% agarose gel to confirm the DNA band.
그 결과, 도 3에 나타난 바와 같이 8마리의 모든 낙지에서 317 bp의 동일한 밴드를 확인할 수 있었다. 이후, 모든 낙지에서 옥토프레신 유전자의 전장 ORF를 포함하는 코딩 서열을 증폭하여 클로닝을 진행하기로 하였다. As a result, as shown in FIG. 3, the same band of 317 bp was confirmed in all eight octopuses. Subsequently, a cloning was performed by amplifying the coding sequence including the full-length ORF of the octopressin gene in all octopuses.
3-3. 옥토프레신 유전자의 코딩 서열 부분 증폭 및 확인3-3. Partial amplification and identification of coding sequence of octopressin gene
옥토프레신의 전장 ORF 코딩 서열을 확보하기 위해 상기 실시예 3-1에서 합성한 cDNA에 프라이머(서열번호 11~12)와 K-2016 AccuPower PCR preMix(Bioneer)를 혼합한 후 옥토프레신 유전자의 전장 코딩 서열에 대해 RT-PCR을 수행(94℃, 10분 → (94℃, 30초 → 60℃, 30 초 → 72℃, 45초) x 30 사이클 → 72℃, 10분 → 10℃ ∞)하였다. 이후, 증폭된 PCR 산물을 1.2% 아가로즈 겔에 전기영동하여 DNA 밴드를 확인하였다. In order to secure the full-length ORF coding sequence of octopressin, the cDNA synthesized in Example 3-1 was mixed with a primer (SEQ ID NOs: 11 to 12) and K-2016 AccuPower PCR preMix (Bioneer) and then the full length of the octopressin gene. RT-PCR was performed on the coding sequence (94 ° C, 10 minutes → (94 ° C, 30 seconds → 60 ° C, 30 seconds → 72 ° C, 45 seconds) x 30 cycles → 72 ° C, 10 minutes → 10 ° C ∞) . Thereafter, the amplified PCR product was electrophoresed on a 1.2% agarose gel to confirm the DNA band.
그 결과, 도 4에 나타난 바와 같이, 모든 낙지에서 687 bp의 동일한 밴드를 확인할 수 있었다. 상기 유전자에 옥토프레신 전장 ORF 코딩 서열이 포함될 것으로 예측하여 이 유전자를 이용하여 클로닝을 진행하였다. As a result, as shown in FIG. 4, it was possible to confirm the same band of 687 bp in all octopuses. The gene was predicted to contain the octopressin full-length ORF coding sequence, and cloning was performed using this gene.
실시예 4. 재조합 유전자의 제조Example 4. Preparation of recombinant gene
4-1. 낙지 유래 재조합 옥토프레신 유전자의 제조4-1. Preparation of recombinant octopressin gene derived from octopus
상기 실시예 3-1의 PCR 산물을 확인한 아가로즈 겔에서 밴드의 위치를 UV로 확인하면서 칼로 잘라냈다. 자른 겔을 을 QIAquick Gel extraction kit(QIAGEN)을 사용하여 밴드 내에 포함되어 있는 증폭된 DNA를 정제하였다. 정제한 PCR 산물 DNA를 pGEM-T easy vector system I (Promega)을 이용하여 벡터에 삽입하고 E.coli DH5α competent cell에 형질전환 한 후, LB/amp 플레이트에서 배양하였다. ligation된 벡터가 형질전환 된 E.coli는 흰색 콜로니로 자라나므로, 낙지 1 마리당 콜로니 5개씩을 골라서 LB/amp 배지에 추가로 배양하였다. 이후, 동일한 콜로니로부터 콜로니 PCR을 수행(95℃, 10분 → (94℃, 30초 → 55℃, 30초 → 72℃ 50초) x 30 사이클 → 72℃, 5분 → 10℃ ∞)하여 배양한 콜로니에 옥토프레신 ORF 코딩 서열이 제대로 삽입되었는지 확인하였다. PCR은 상용화된 sp6 프라이머와 T7 프라이머를 첨가하여 진행하였다. 이후, 증폭된 PCR 산물을 1% 아가로즈 겔에 전기영동하여 확인하였다.In the agarose gel confirming the PCR product of Example 3-1, the band was cut with a knife while confirming the position of the band with UV. The amplified DNA contained in the band was purified using the QIAquick Gel extraction kit (QIAGEN). The purified PCR product DNA was inserted into a vector using pGEM-T easy vector system I (Promega), transformed into E.coli DH5α competent cells, and cultured in an LB / amp plate. E.coli transformed with the ligated vector grows into white colonies, so 5 colonies per octopus were selected and further cultured in LB / amp medium. Then, colony PCR was performed from the same colony (95 ° C, 10 minutes → (94 ° C, 30 seconds → 55 ° C, 30 seconds → 72 ° C, 50 seconds) x 30 cycles → 72 ° C, 5 minutes → 10 ° C ∞) and cultured It was confirmed that the octopressin ORF coding sequence was correctly inserted in one colony. PCR was performed by adding commercialized sp6 primer and T7 primer. Then, the amplified PCR product was confirmed by electrophoresis on a 1% agarose gel.
그 결과, 도 5에 나타난 바와 같이, 벡터에 옥토프레신 코딩 서열이 삽입된 재조합 플라스미드 DNA는 837bp의 밴드를 나타내고 백터가 self-ligation된 재조합 플라스미드 DNA는 150bp의 밴드를 나타냄을 확인할 수 있었다. As a result, as shown in FIG. 5, it was confirmed that the recombinant plasmid DNA in which the octopressin coding sequence was inserted into the vector represents a band of 837 bp, and the recombinant plasmid DNA in which the vector was self-ligated represents a 150 bp band.
4-2. 재조합 옥토프레신 유전자의 코딩 염기서열 확인4-2. Confirm the coding sequence of the recombinant octopressin gene
상기 실시예 4-1에서 배양한 E.coli 중 837bp를 밴드를 나타내는, 즉 옥토프레신 코딩 서열이 삽입된 콜로니를 낙지 1 마리당 2개씩 선택한 후, QIAprep spin miniprep kit(QIAGEN)을 이용하여 플라스미드 DNA를 추출하였다. 이후, 추출한 DNA의 농도를 측정하고 염기서열을 분석하여 옥토프레신 전장 코딩 서열을 포함하고 있는지 확인하고 상기 실시예 2에서 예측한 염기서열을 검증하였다. 이때, 상기 실시예 2-2에서 사용한 것과 동일한 프라이머를 사용하였고 마크로젠에 의뢰하여 염기서열을 분석하였다. 이후, 분석한 결과를 MEGA6 프로그램을 사용하여 정렬하였다. Plasmid DNA by using QIAprep spin miniprep kit (QIAGEN) after selecting 2 colonies each octopus which represents the band of 837 bp of E. coli cultured in Example 4-1, i.e., octopressin coding sequence is inserted. Was extracted. Subsequently, the concentration of the extracted DNA was measured and the base sequence was analyzed to confirm whether it contained the octopressin full-length coding sequence, and the base sequence predicted in Example 2 was verified. At this time, the same primers used in Example 2-2 were used, and the base sequence was analyzed by requesting Macrogen. Thereafter, the analyzed results were sorted using the MEGA6 program.
그 결과, 도 6에 나타난 바와 같이, 클로닝한 부분의 염기서열은 대부분 일치하였다. 변이가 발생한 서열도 발견되었으나 ORF 부위의 염기서열 개수는 8마리의 낙지에서 모두 동일하였다. 또한, 옥토프레신 활성 펩타이드(9개의 아미노산)와 시그널 펩타이드에 해당하는 부분은 8마리 낙지의 염기서열이 모두 동일함을 확인하였고, 상기 실시예 2-2에서 유전체 분석을 통해 예측한 서열과 정확히 일치하는 것을 확인할 수 있었다. 뉴로피신과 글리코펩타이드에 해당하는 부분은 염기서열의 개수는 동일하였으나, 염기서열에 낙지 개체간 차이가 발견되었다. 상기와 같은 결과로 보아, 8마리의 낙지로부터 옥토프레신 전장 코딩서열을 포함하는 재조합 플라스미드 DNA를 성공적으로 제조하였음을 확인할 수 있다. As a result, as shown in Fig. 6, the base sequences of the cloned parts were mostly identical. Sequences with mutations were also found, but the number of nucleotide sequences in the ORF site was the same in all eight octopuses. In addition, the octopresin active peptide (9 amino acids) and the part corresponding to the signal peptide were confirmed to have the same base sequence of all 8 octopus, and exactly the sequence predicted through genomic analysis in Example 2-2. It was confirmed that they match. The number of nucleotide sequences in the parts corresponding to neuropicine and glycopeptide was the same, but differences between octopus individuals were found in the nucleotide sequence. As a result of the above, it can be confirmed that the recombinant plasmid DNA including the octopressin full-length coding sequence was successfully prepared from eight octopuses.
실시예 5. 옥토프레신 펩타이드의 생체 활성 분석Example 5. Analysis of bioactivity of octopressin peptide
상기 실시예 4에서 예측한 옥토프레신 아미노산 서열 및 변형(modification)을 만족하는 펩타이드를 합성 업체에 주문하여 구입하여 사용하였다. 건조된 펩타이드 가루를 3차 증류수에 10㎎/㎖이 되도록 녹이고 0.20㎛ 필터에 여과한 인공 해수의 100배로 희석하여 주사 용액을 만들었다. 일회용 주사기와 26 gauge 주사바늘을 이용하여 1㎝ 깊이로 찌른 후 성체 낙지와 머리의 몸 사이 정 중앙에 주사용액을 투여하였다. 주사량은 낙지의 무게를 재어 100 microgram/㎏씩이 되도록 하였다. 대조군으로는 아무것도 주사하지 않은 낙지(주사 전), 여과한 인공 해수만 주사한 낙지 및 문어 유래 옥토프레신을 주사한 낙지를 사용하였다.Peptides satisfying the octopressin amino acid sequence and modification (modification) predicted in Example 4 were ordered from a synthetic company and used. The dried peptide powder was dissolved in tertiary distilled water to a concentration of 10 mg / mL and diluted with a 0.20 µm filter to 100 times of artificial seawater filtered to make an injection solution. After using a disposable syringe and a 26 gauge injection needle, it was poked to a depth of 1 cm and the injection solution was administered at the center of the body between the adult octopus and the head. The injection volume was weighed by the octopus so that it was 100 microgram / kg. As a control group, octopus injected with nothing (before injection), octopus injected with filtered artificial seawater and octopus derived from octopus were used.
도 8a는 펩타이드 주사 후 낙지의 행동 변화를 나타내는 사진이다. 도 8a에 나타난 바와 같이, 펩타이드를 주사한 낙지에서 여러 개의 팔(다리)을 구부렸다 펴는 반복적인 움직임을 관찰하였고, 다른 낙지에 접근하거나 팔(다리)을 뻗어 건드리고 닦아주는 듯한 사회적 행동이 유도되는 것을 관찰할 수 있었다. 또한, 상기와 같은 행동 변화는 주사 후 1~5분이 경과한 후에 나타나기 시작하여 10~20분 동안 지속되었으며 효과는 주사 후 5~10분 사이에 최고조에 달했고, 10~20분 동안 지속되었다. 하루에 1~3마리, 총 12마리의 낙지에서 옥토프레신 활성 펩타이드가 암수 성별에 관계없이 생체 활성을 가지는 것을 확인하였다. 이때, 사용한 낙지는 재사용하지 않고 폐기하였다. 반면, 아무것도 주사하지 않은 낙지와 여과한 인공 해수만을 주사한 낙지 및 문어 유래 옥토프레신을 주사한 낙지에서는 특별한 행동 변화를 관찰할 수 없었다. 8A is a photograph showing changes in octopus behavior after peptide injection. As shown in FIG. 8A, repeated movements of bending and stretching several arms (legs) in an octopus injected with peptides were observed, and social behaviors such as touching and wiping the arms (legs) approaching other octopuses were induced. I could observe. In addition, the above behavioral change began to appear after 1-5 minutes after injection, and lasted for 10-20 minutes, and the effect reached a peak between 5-10 minutes after injection, and lasted for 10-20 minutes. It was confirmed that 1 to 3 animals per day, a total of 12 octopuses, the octopressin-activated peptide had bioactivity regardless of sex. At this time, the octopus used was discarded without being reused. On the other hand, no special behavioral changes could be observed in the octopus injected with nothing, the octopus injected with octopus derived from octopus, and the octopus injected only with filtered artificial seawater.
도 8b는 옥토프레신을 주사한 낙지가 포란 행동과 유사한 행동을 나타냄을 관찰한 사진이다. 도 8b에 나타난 바와 같이, 낙지 유래 옥토프레신은 낙지에서 포란 행동 유사 행동 및 사회적 행동을 유도할 수 있는바, 교미를 촉진하고 더 많은 낙지 알을 부화시킴으로써 낙지 생산량을 증대시킬 수 있는바, 낙지 자원의 증식에 이용될 수 있다. FIG. 8B is a photograph observing that octopus injected with octopressin exhibits a behavior similar to that of a porosity. As shown in FIG. 8B, octopus derived from octopus can induce behavioral behavior and social behavior similar to octopus in octopus, which can increase octopus production by promoting mating and hatching more octopus eggs, octopus resources It can be used for multiplication.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.The above description of the present invention is for illustration only, and a person having ordinary knowledge in the technical field to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive.
<110> National Marine Biodiversity Institute of Korea <120> Active peptide of Octopus minor octopressin, and uses thereof <130> PN123184 <160> 12 <170> KoPatentIn 3.0 <210> 1 <211> 985 <212> DNA <213> Artificial Sequence <220> <223> Fal62_P1_07228_Octopressin <400> 1 gagagaagat atctagtagc cgtcagtgtc acacgaagac acctacatta gtaaaaccta 60 gaataaatct agaaaaggct actttgatag atcaaccaat gaaacgagct aactgtgaac 120 taactagcca atcatatatt tgcaaatttt aaaagacaca acaagataaa ccaaagaaga 180 gaaaacaaca aaataaaaca agaaaaataa ccgattaaaa cgagatcaga acctccctaa 240 ccaaatcata aataacgtaa aataatcgaa taaaagttgt acgaaatcta ggctaagtct 300 accgaatttg tgtacaacaa gaaaaataac tacaacgata agaaaaaaaa ccccaaaaaa 360 cccaaaatac tgaagcgaat ttcaaggaaa tattcccgtg aaaccggaaa aaaaaagata 420 cggaaccagc aatattaaaa gagctgaata ctaaacaaga gttttaatag aaacacacac 480 atatatacat atatatatat atatataact tgatcccccc aaaacttcta aaataaactt 540 agaaaaaatg gcgagtttaa aaagtagtgt ttttgcaatt ttaattgttg tcgtacttct 600 acctattgtg agaagttgtt tctggacaaa ctgccctgtt ggtggcaaaa gaagtaatat 660 acctgcagct gaaccaagaa agtgtatgtc ctgcggaccc aaaggtgaag gccagtgtgt 720 tggacccaac atttgctgcc acaaagacgg ttgtatcata ggcttacttg gaaaagaatg 780 caatgctgaa aacgagagta cgacaccatg ttctgtgaca gctgcctgct cttcgaacac 840 tcgctgtaac accagtggag gccgtagtaa gagtctgaaa gaattacttg cggttctaaa 900 caaaatatgt gacaaagtga atcatcgcag catcgcgatg cagaaattat tggcaatgcg 960 agatggattt tattacaaga aataa 985 <210> 2 <211> 145 <212> PRT <213> Artificial Sequence <220> <223> Octopressin_ORF2 <400> 2 Met Ala Ser Leu Lys Ser Ser Val Phe Ala Ile Leu Ile Val Val Val 1 5 10 15 Leu Leu Pro Ile Val Arg Ser Cys Phe Trp Thr Asn Cys Pro Val Gly 20 25 30 Gly Lys Arg Ser Asn Ile Pro Ala Ala Glu Pro Arg Lys Cys Met Ser 35 40 45 Cys Gly Pro Lys Gly Glu Gly Gln Cys Val Gly Pro Asn Ile Cys Cys 50 55 60 His Lys Asp Gly Cys Ile Ile Gly Leu Leu Gly Lys Glu Cys Asn Ala 65 70 75 80 Glu Asn Glu Ser Thr Thr Pro Cys Ser Val Thr Ala Ala Cys Ser Ser 85 90 95 Asn Thr Arg Cys Asn Thr Ser Gly Gly Arg Ser Lys Ser Leu Lys Glu 100 105 110 Leu Leu Ala Val Leu Asn Lys Ile Cys Asp Lys Val Asn His Arg Ser 115 120 125 Ile Ala Met Gln Lys Leu Leu Ala Met Arg Asp Gly Phe Tyr Tyr Lys 130 135 140 Lys 145 <210> 3 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Octopressin_active peptide <400> 3 Cys Phe Trp Thr Asn Cys Pro Val Gly 1 5 <210> 4 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> homo sapiens_oxytocin <400> 4 Cys Tyr Ile Gln Asn Cys Pro Leu Gly 1 5 <210> 5 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> homo sapiens_vasopressin <400> 5 Cys Tyr Pro Gln Asn Cys Pro Arg Gly 1 5 <210> 6 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> octopus vulgaris_octopressin <400> 6 Cys Phe Trp Thr Ser Cys Pro Ile Gly 1 5 <210> 7 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Octopus vulgaris_cephalotocin <400> 7 Cys Tyr Phe Arg Asn Cys Pro Ile Gly 1 5 <210> 8 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Sepia officinalis_sepiatocin <400> 8 Cys Phe Trp Thr Thr Cys Pro Ile Gly 1 5 <210> 9 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Om-S011E-F1 <400> 9 gttgtttctg gacaaactgc c 21 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Om-S011E-R1 <400> 10 gctgcgatga ttcactttgt c 21 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Om-S011C-F1 <400> 11 ggaaatattc ccgtgaaacc 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Om-S011C-R1 <400> 12 cattttgctg atgagggtag 20 <110> National Marine Biodiversity Institute of Korea <120> Active peptide of Octopus minor octopressin, and uses thereof <130> PN123184 <160> 12 <170> KoPatentIn 3.0 <210> 1 <211> 985 <212> DNA <213> Artificial Sequence <220> <223> Fal62_P1_07228_Octopressin <400> 1 gagagaagat atctagtagc cgtcagtgtc acacgaagac acctacatta gtaaaaccta 60 gaataaatct agaaaaggct actttgatag atcaaccaat gaaacgagct aactgtgaac 120 taactagcca atcatatatt tgcaaatttt aaaagacaca acaagataaa ccaaagaaga 180 gaaaacaaca aaataaaaca agaaaaataa ccgattaaaa cgagatcaga acctccctaa 240 ccaaatcata aataacgtaa aataatcgaa taaaagttgt acgaaatcta ggctaagtct 300 accgaatttg tgtacaacaa gaaaaataac tacaacgata agaaaaaaaa ccccaaaaaa 360 cccaaaatac tgaagcgaat ttcaaggaaa tattcccgtg aaaccggaaa aaaaaagata 420 cggaaccagc aatattaaaa gagctgaata ctaaacaaga gttttaatag aaacacacac 480 atatatacat atatatatat atatataact tgatcccccc aaaacttcta aaataaactt 540 agaaaaaatg gcgagtttaa aaagtagtgt ttttgcaatt ttaattgttg tcgtacttct 600 acctattgtg agaagttgtt tctggacaaa ctgccctgtt ggtggcaaaa gaagtaatat 660 acctgcagct gaaccaagaa agtgtatgtc ctgcggaccc aaaggtgaag gccagtgtgt 720 tggacccaac atttgctgcc acaaagacgg ttgtatcata ggcttacttg gaaaagaatg 780 caatgctgaa aacgagagta cgacaccatg ttctgtgaca gctgcctgct cttcgaacac 840 tcgctgtaac accagtggag gccgtagtaa gagtctgaaa gaattacttg cggttctaaa 900 caaaatatgt gacaaagtga atcatcgcag catcgcgatg cagaaattat tggcaatgcg 960 agatggattt tattacaaga aataa 985 <210> 2 <211> 145 <212> PRT <213> Artificial Sequence <220> <223> Octopressin_ORF2 <400> 2 Met Ala Ser Leu Lys Ser Ser Val Phe Ala Ile Leu Ile Val Val Val 1 5 10 15 Leu Leu Pro Ile Val Arg Ser Cys Phe Trp Thr Asn Cys Pro Val Gly 20 25 30 Gly Lys Arg Ser Asn Ile Pro Ala Ala Glu Pro Arg Lys Cys Met Ser 35 40 45 Cys Gly Pro Lys Gly Glu Gly Gln Cys Val Gly Pro Asn Ile Cys Cys 50 55 60 His Lys Asp Gly Cys Ile Ile Gly Leu Leu Gly Lys Glu Cys Asn Ala 65 70 75 80 Glu Asn Glu Ser Thr Thr Pro Cys Ser Val Thr Ala Ala Cys Ser Ser 85 90 95 Asn Thr Arg Cys Asn Thr Ser Gly Gly Arg Ser Lys Ser Leu Lys Glu 100 105 110 Leu Leu Ala Val Leu Asn Lys Ile Cys Asp Lys Val Asn His Arg Ser 115 120 125 Ile Ala Met Gln Lys Leu Leu Ala Met Arg Asp Gly Phe Tyr Tyr Lys 130 135 140 Lys 145 <210> 3 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Octopressin_active peptide <400> 3 Cys Phe Trp Thr Asn Cys Pro Val Gly 1 5 <210> 4 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> homo sapiens_oxytocin <400> 4 Cys Tyr Ile Gln Asn Cys Pro Leu Gly 1 5 <210> 5 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> homo sapiens_vasopressin <400> 5 Cys Tyr Pro Gln Asn Cys Pro Arg Gly 1 5 <210> 6 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> octopus vulgaris_octopressin <400> 6 Cys Phe Trp Thr Ser Cys Pro Ile Gly 1 5 <210> 7 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Octopus vulgaris_cephalotocin <400> 7 Cys Tyr Phe Arg Asn Cys Pro Ile Gly 1 5 <210> 8 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Sepia officinalis_sepiatocin <400> 8 Cys Phe Trp Thr Thr Cys Pro Ile Gly 1 5 <210> 9 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Om-S011E-F1 <400> 9 gttgtttctg gacaaactgc c 21 <210> 10 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Om-S011E-R1 <400> 10 gctgcgatga ttcactttgt c 21 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Om-S011C-F1 <400> 11 ggaaatattc ccgtgaaacc 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Om-S011C-R1 <400> 12 cattttgctg atgagggtag 20
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|---|---|---|---|---|
| JP2001527537A (en) * | 1997-03-27 | 2001-12-25 | エントレテク メディカル アクチボラゲット | Use of a substance having oxytocin activity for the manufacture of a medicament for the treatment of affective pain syndrome |
| JP2003047475A (en) * | 2001-08-03 | 2003-02-18 | Suntory Ltd | Novel peptide classified into oxytocin/vasopressin superfamily, precursor peptide thereof and genes encoding the same |
| KR100763938B1 (en) * | 2004-12-30 | 2007-11-28 | 부경대학교 산학협력단 | Hydrolysates from Alaska pollack frame |
| WO2016140063A1 (en) * | 2015-03-04 | 2016-09-09 | 栄研化学株式会社 | Method for measuring oxytocin with high sensitivity |
-
2018
- 2018-10-24 KR KR1020180127704A patent/KR102193195B1/en active IP Right Grant
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001527537A (en) * | 1997-03-27 | 2001-12-25 | エントレテク メディカル アクチボラゲット | Use of a substance having oxytocin activity for the manufacture of a medicament for the treatment of affective pain syndrome |
| JP2003047475A (en) * | 2001-08-03 | 2003-02-18 | Suntory Ltd | Novel peptide classified into oxytocin/vasopressin superfamily, precursor peptide thereof and genes encoding the same |
| KR100763938B1 (en) * | 2004-12-30 | 2007-11-28 | 부경대학교 산학협력단 | Hydrolysates from Alaska pollack frame |
| WO2016140063A1 (en) * | 2015-03-04 | 2016-09-09 | 栄研化学株式会社 | Method for measuring oxytocin with high sensitivity |
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