MARINE CYSTINE KNOT PEPTIDES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 从一种独特的海洋无脊椎动物中分离出了一种具有独特焦谷氨酸N-末端的35个残基的胱氨酸结肽，该海洋无脊椎动物在分类学上不同于众所周知的产生芋螺毒素的锥螺。 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，这类肽一直是药物发现界的重大兴趣。 该肽的详细结构归属对于与已知的胱氨酸结肽如芋螺毒素和各种陆地毒液进行比较以确定其是否可能与已知的生物靶标具有任何相互作用将是重要的。 人们曾尝试过包括酶法和部分还原/烷基化在内的化学方法来确定二硫键的位置，但都失败了。 除了改善肽的整体预测外，高场NMR还将提供必要的分辨率来确定关键结构特征的排列。

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.