MARINE CYSTINE KNOT PEPTIDES

海洋胱氨酸结肽

• 批准号: 8361215
• 负责人: Mark T Hamann
• 金额: $ 3.3万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361215
• 关键词: Alkylation; Biological; Chemicals; Communities; Computer Simulation; Conotoxin; Cystine; Funding; Grant; Location; Marine Invertebrates; Methods; National Center for Research Resources; Peptides; Principal Investigator; Pyrrolidonecarboxylic Acid; Research; Research Infrastructure; Resolution; Resources; Retinal Cone; Snails; Source; Structure; United States National Institutes of Health; Venoms; cost; drug discovery; improved; interest; microbial

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A 35-residue cystine knot peptide with a unique pyroglutamic acid N-terminus has been isolated from a unique marine invertebrate taxonomically distinct from the well known conotoxin producing cone snails. This discovery provides strong evidence for a microbial symbiont that produces this class of peptide which has been of significant interest to the drug discovery community. The detailed structure assignment of this peptide will be important for comparison to known cystine knot peptides like the conotoxins and various terrestrial venoms to determine if it may have any interactions with known biological targets. Chemical methods including enzymatic and partial reductions/alkylations have been attempted to establish the locations of the dissulfide linkages but have failed. In addition to improving the overall prediction of the peptide in silico, high field NMR will provide the necessary resolution to determine the arrangements of critical structural features.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 一种具有独特焦谷氨酸 N 末端的 35 残基胱氨酸结肽已从一种独特的海洋无脊椎动物中分离出来，该无脊椎动物在分类学上与众所周知的产生芋螺毒素的锥螺不同。 这一发现为产生这类肽的微生物共生体提供了强有力的证据，这种肽一直引起药物发现界的极大兴趣。 该肽的详细结构分配对于与已知的胱氨酸结肽（如芋螺毒素和各种陆生毒液）进行比较非常重要，以确定它是否可能与已知的生物靶标有任何相互作用。 已尝试包括酶促和部分还原/烷基化在内的化学方法来确定二硫键的位置，但失败了。 除了改进计算机中肽的整体预测之外，高场核磁共振还将提供必要的分辨率来确定关键结构特征的排列。