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Myomodulin E 및 유도체들의 합성 및 생리활성

Synthesis and Biological Activities of Myomodulin E and its Analogs

  • 고혜진 (부경대학교 수산과학대학 생물공학과) ;
  • 서정길 (부경대학교 수산과학대학 생물공학과) ;
  • 서혜점 (부경대학교 수산과학대학 생물공학과) ;
  • 이민정 (부경대학교 수산과학대학 생물공학과) ;
  • 박태현 (웨스트밴쿠버고등학교) ;
  • 김군도 (부경대학교 자연과학대학 미생물학과) ;
  • 박남규 (부경대학교 수산과학대학 생물공학과)
  • Go, Hye-Jin (Department of Biotechnology, Fisheries Science College, Pukyong National University) ;
  • Seo, Jung-Kil (Department of Biotechnology, Fisheries Science College, Pukyong National University) ;
  • Seo, Hae-Jeom (Department of Biotechnology, Fisheries Science College, Pukyong National University) ;
  • Lee, Min-Jeong (Department of Biotechnology, Fisheries Science College, Pukyong National University) ;
  • Park, Tae-Hyun (West Vancouver Secondary School) ;
  • Kim, Gun-Do (Department of Microbilogy, Natural Science College, Pukyong National University) ;
  • Park, Nam-Gyu (Department of Biotechnology, Fisheries Science College, Pukyong National University)
  • 투고 : 2011.12.21
  • 심사 : 2012.01.25
  • 발행 : 2012.04.30

초록

군소인 Aplysia kurodai의 중추신경절로부터 발견된 myomodulin A (MMA, PMSMLRLamide)와 myomodulin E (MME, GLQMLRLamide)는 $Mytilus$ $edulis$의 anterior byssus retractor muscle (ABRM)을 활성측정시스템으로 사용하여 정제되었다. 정제된 MMA와 MME는 연체동물에서 발견된 myomodulin 계열의 펩타이드와 동일한 일차구조를 지닌다. MME의 구조와 활성간의 상관관계를 알아보기 위해서 MME, 유도체 및 다른 신경성 펩타이드들을 합성하였다. MME의 유도체인 Des[$Gly^1$]-MME, Des[$Gly^1,Leu^2$]-MME 및 Des[$Gly^1,Leu^2,Gln^3$]-MME의 일차구조는 각각 LQMLRLamide, QMLRLamide 및 MLRLamide이다. 합성 물질들을 사용하여 ABRM에 대한 phasic contraction을 측정하였다. MME는 $1{\times}10^{-9}$ M 또는 더 높은 농도에서 ABRM의 phasic contraction을 저해하였다. 또한 MME는 $1{\times}10^{-8}$ M에서 catch-tension에 대해 이완활성을 나타내었다. 합성 펩타이드들을 사용하여 Africa giant snail, $Achatina$ $fulica$의 소낭과 penial retractor muscle에 대해서도 활성을 측정하였다. MME와 유도체들은 소낭에 대해서는 수축반응을 보였지만, penial retractor muscle에 대해서는 이완 활성을 나타내었다. 이러한 결과들은 MME와 그 유도체들은 연체동물의 다양한 조직에 대해 조절 효과를 가지고 있다는 것을 의미한다. 본 연구는 생체 내에서 발생하는 신경 및 circuit의 변화를 조절하는 작용 연구에 대한 기본적인 자료가 될 것이다.

Previous work has characterized myomodulin A (MMA, PMSMLRLamide) and myomodulin E (MME, GLQMLRLamide) purified from the central nervous systems of the sea hare, $Aplysia$ $Kurodai$, using the anterior byssus retractor muscle (ABRM) of the mussel, $Mytilus$ $edulis$. The amino acid sequences of MMA and MME were the same as those of the myomodulin family peptide found in other mollusks. In this study, we synthesized MME, its derivatives, and other neuropeptides to investigate the relationship between the structure and biological activity of MME. The primary structures of MME's derivatives, Des[$Gly^1$]-MME, Des[$Gly^1,Leu^2$]-MME, and Des[$Gly^1,Leu^2,Gln^3$]-MME, were LQMLRLamide, QMLRLamide, and MLRLamide, respectively. MMA and synthetic peptides were tested on ABRM in $M.$ $edulis$ as well as muscle preparations in $Achatina$ $fulica$. MME displayed an inhibitory effect on phasic contraction of the ABRM at $1{\times}10^{-9}$ M or higher. MME also had a relaxing effect on the catch-tension of AMRM at $1{\times}10^{-8}$ M. Both MMA and its analogs stimulated a contractile response on the crop and relaxed the catch-relaxing response on the penial retractor muscle of $A.$ $fulica$. These results suggest that MME and its analogs have modulatory effects on various muscles of mollusks. This study has also laid the groundwork for future neural and circuit modulation studies during animal behavioral changes.

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참고문헌

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