Dugas H, Laroche M, Ptak M, Labbé H
Department of Chemistry, University of Montreal, Quebec, Canada.
Int J Pept Protein Res. 1993 Jun;41(6):595-605. doi: 10.1111/j.1399-3011.1993.tb00482.x.
The tripeptide N-formyl-Met-Pro-Phe-OMe (f-MPF-OMe), an analogue of the signal peptide N-formyl-Met-Leu-Phe-OH (f-MLF-OH), was synthesized and its chemotactic activity evaluated; it showed no activity in either superoxide production or calcium mobility with human neutrophils. However, the corresponding acid f-MPF-OH retained about 25% activity in the production of superoxide. The conformation of the f-MPF-OMe analogue was evaluated by NMR spectroscopy and molecular simulation and shown to predominate in a gamma-turn with a hydrogen bond between Met CO and Phe NH. Since this analogue is not chemotactic, it is suggested that for recognition the receptor prefers a peptide with a flexible backbone, favoring an extended conformation in the binding site.
合成了信号肽N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（f-MLF-OH）的类似物三肽N-甲酰甲硫氨酰-脯氨酰-苯丙氨酸甲酯（f-MPF-OMe），并评估了其趋化活性；在人中性粒细胞的超氧化物生成或钙迁移方面，它均无活性。然而，相应的酸f-MPF-OH在超氧化物生成方面保留了约25%的活性。通过核磁共振光谱和分子模拟对f-MPF-OMe类似物的构象进行了评估，结果表明其主要以γ-转角构象为主，甲硫氨酸羰基（Met CO）和苯丙氨酸氨基（Phe NH）之间存在氢键。由于该类似物没有趋化作用，因此有人提出，为了实现识别，受体更喜欢具有柔性主链的肽，有利于在结合位点形成伸展构象。
