Benaki Dimitra, Zikos Christos, Evangelou Alexandra, Livaniou Evangelia, Vlassi Metaxia, Mikros Emmanuel, Pelecanou Maria
Institute of Biology, NCSR Demokritos 15310 Athens, Greece.
Biochem Biophys Res Commun. 2006 Oct 20;349(2):634-42. doi: 10.1016/j.bbrc.2006.08.087. Epub 2006 Aug 23.
The NMR solution study of Ser14Gly-humanin (S14G-HN), a 1000-fold more potent derivative of humanin (HN), is reported. HN is 24-residue peptide that selectively suppresses neuronal cell death caused by Alzheimer's disease (AD)-specific insults and offers hope for the development of a cure against AD. In aqueous solution the NMR data show that S14G-HN is a flexible peptide with turn-like structures in its conformational ensemble distributed over an extensive part of its sequence from Pro3 to Glu15. In the more lipophilic environment of 30% TFE, an alpha-helical structure spanning residues Phe6 to Thr13 is identified. Comparison of these findings to the NMR structure of the parent HN and to existing structure-function relationship literature data outlines the important for activity structural features for this class of neuroprotective peptides, and brings forth flexibility as an important characteristic that may facilitate interactions with functional counterparts of the neuroprotection pathway.
本文报道了人胰岛素原（HN）的一种活性增强1000倍的衍生物——Ser14Gly-人胰岛素原（S14G-HN）的核磁共振溶液研究。HN是一种由24个氨基酸组成的肽，它能选择性地抑制由阿尔茨海默病（AD）特异性损伤引起的神经元细胞死亡，为开发治疗AD的药物带来了希望。在水溶液中，核磁共振数据表明S14G-HN是一种柔性肽，其构象集合中具有类似转角的结构，分布在从Pro3到Glu15的序列的大部分区域。在30%TFE的更亲脂性环境中，鉴定出了一个跨越Phe6到Thr13残基的α-螺旋结构。将这些发现与母体HN的核磁共振结构以及现有的结构-功能关系文献数据进行比较，概述了这类神经保护肽活性结构特征的重要性，并提出了柔性作为一个重要特征，可能有助于与神经保护途径的功能对应物相互作用。
