Cyclisation Increases the Stability of the Sea Anemone Peptide APETx2 but Decreases Its Activity at Acid-Sensing Ion Channel 3
作者: Lachlan D. RashGlenn F. KingPaul F. AlewoodMehdi MobliAndreas BrustJonas E. Jensen
刊名: Marine Drugs, 2012, Vol.10 (7), pp.1511-1527
来源数据库: Directory of Open Access Journals
DOI: 10.3390/md10071511
关键词: Sea anemonePeptideAPETx2ASIC3CyclisationTruncationStability
原始语种摘要: APETx2 is a peptide isolated from the sea anemone Anthopleura elegantissima . It is the most potent and selective inhibitor of acid-sensing ion channel 3 (ASIC3) and it is currently in preclinical studies as a novel analgesic for the treatment of chronic inflammatory pain. As a peptide it faces many challenges in the drug development process, including the potential lack of stability often associated with therapeutic peptides. In this study we determined the susceptibility of wild-type APETx2 to trypsin and pepsin and tested the applicability of backbone cyclisation as a strategy to improve its resistance to enzymatic degradation. Cyclisation with either a six-, seven- or eight-residue linker vastly improved the protease resistance of APETx2 but substantially decreased its potency against...
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影响因子:3.978 (2012)

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关键词翻译
关键词翻译
  • linker 链接编辑程序
  • terminus 末端
  • anemone 银莲花属
  • either 任何
  • ASIC application specific integrated circuit
  • unlikely 不可能的
  • confirmed 已确认的
  • eight 
  • applicability 适用性
  • involved 涉及