Novel natriuretic peptides from the venom of the inland taipan (Oxyuranus microlepidotus):: isolation, chemical and biological characterisation

Novel natriuretic peptides from the venom of the inland taipan (Oxyuranus microlepidotus):: isolation, chemical and biological characterisation
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DOI:
10.1016/j.bbrc.2004.11.171
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发表时间:
2005-02-25
影响因子:
3.1
通讯作者:
Alewood, P
Alewood, P
中科院分区:
生物学4区
文献类型:
--
作者:
Fry, BG;Wickramaratana, JC;Alewood, P

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从细鳞尖尾蜥(Oxyuranus microlepidotus)(内陆太攀蛇)毒液中分离到三种利尿钠样肽(TNP-a、TNP-b和TNP-c),在小盾尖尾蜥(Oxyuranus scutellatus canni)(新几内亚太攀蛇)和小盾尖尾蜥(Oxyuranus scutellatus scutellatus)(沿海太攀蛇)毒液中也存在。它们通过HPLC分离,通过质谱和Edman分析表征,并且由35-39个氨基酸残基组成。这些分子与ANP/BNP的不同之处在于17元环结构内的不变残基的替换和C-末端尾中的脯氨酸残基的包含。在特异性GC-A测定或主动脉环测定中,TNP-c与ANP等效,而TNP-a和TNP-b无活性(GC-A过表达细胞和内皮剥脱的主动脉环)或弱活性(内皮完整的主动脉环)。TNP-a和TNP-b也不能竞争性地抑制内皮剥脱的血管(GC-A)或内皮完整的血管(NPR-C)中TNP-c的结合。因此,这些天然存在的异构体提供了一个新的平台,进一步研究的结构与功能的关系的利钠肽。(C)2004年爱思唯尔公司All rights reserved.
Three natriuretic-like peptides (TNP-a, TNP-b, and TNP-c) were isolated from the venom of Oxyuranus microlepidotus (inland taipan) and were also present in the venoms of Oxyuranus scutellatus canni (New Guinea taipan) and Oxyuranus scutellatus scutellatus (coastal taipan). They were isolated by HPLC, characterised by mass spectrometry and Edman analysis, and consist of 35-39 amino acid residues. These molecules differ from ANP/BNP through replacement of invariant residues within the 17-membered ring structure and by inclusion of proline residues in the C-terminal tail. TNP-c was equipotent to ANP in specific GC-A assays or aortic ring assays whereas TNP-a and TNP-b were either inactive (GC-A over-expressing cells and endothelium-denuded aortic rings) or weakly active (endothelium-in tact aortic rings). TNP-a and TNP-b were also unable to competitively inhibit the binding of TNP-c in endothelium-denuded aortae (GC-A) or endothelium-in tact aortae (NPR-C). Thus, these naturally occurring isoforms provide a new platform for further investigation of structure-function relationships of natriuretic peptides. (C) 2004 Elsevier Inc. All rights reserved.