Lombardi A, D'Auria G, Saviano M, Maglio O, Nastri F, Quartara L, Pedone C, Pavone V
Centro Interdipartimentale di Ricerca sui Peptidi Bioattivi CEINGE--Biotecnologie Avanzate, Napoli, Italy.
Biopolymers. 1996;40(5):505-18. doi: 10.1002/(sici)1097-0282(1996)40:5<505::aid-bip8>3.0.co;2-#.
We recently reported the rational design, synthetics, and structural characterization of the most potent and selective peptide-based neurokinin A antagonist thus far described: cyclo(Met1-Asp2-Trp3-Phe4-Dap5-Leu6)cyclo(2 beta-5 beta). Its bicyclic structure is characterized by a type I and a type II two beta-turn around Trp3-Phe4 and Leu6-Met1, respectively. In order to understand whether the two different beta-turned structures are determined by the bicyclic structure or by the amino acid type at the corner positions, we have synthesized the pseudo-symmetrical analogue cyclo(Phe1-Asp2-Trp3-Phe4-Dap5-Trp6)cyclo(2 beta-5 beta). The structural characterization in the crystal state and in solution, here reported, gives an experimental evidence that the backbone of the bicyclic structure is a rigid scaffold that can be used to build both a type I and type II beta-turn independently from the amino acid composition.
我们最近报道了迄今为止所描述的最有效且最具选择性的基于肽的神经激肽A拮抗剂的合理设计、合成及结构表征：环（Met1-Asp2-Trp3-Phe4-Dap5-Leu6）环（2β-5β）。其双环结构的特征分别是在Trp3-Phe4和Leu6-Met1周围存在一个I型和一个II型双β-转角。为了了解这两种不同的β-转角结构是由双环结构决定还是由转角位置的氨基酸类型决定，我们合成了假对称类似物环（Phe1-Asp2-Trp3-Phe4-Dap5-Trp6）环（2β-5β）。此处报道的在晶体状态和溶液中的结构表征提供了实验证据，表明双环结构的主链是一个刚性支架，可独立于氨基酸组成用于构建I型和II型β-转角。
