肠抑胃素生物活性的结构要求

Structural requirements for the biological activity of enterostatin.

作者信息

Lin L, Okada S, York D A, Bray G A

机构信息

Pennington Biomedical Research Center, Baton Rouge, LA 70808.

出版信息

Peptides. 1994;15(5):849-54. doi: 10.1016/0196-9781(94)90041-8.

DOI:10.1016/0196-9781(94)90041-8

PMID:7984504

Abstract

A series of enterostatin analogues were tested to investigate the minimal structure required for activity to suppress the intake of high-fat (HF) diets. The dose-response curve to intracerebroventricular (ICV) enterostatin was U-shaped (maximal inhibition at 1 nmol). Removal or modification of the N-terminal valine from enterostatin (Val-Pro-Asp-Pro-Arg) abolished activity, as did C-terminal amidation. The tripeptide (Pro-Asp-Pro) and the cyclo-diketopiperazine cyclo-Asp-Pro retained activity whereas the linear Asp-Pro dipeptide was inactive. In rats adapted to a three-choice macronutrient diet, cyclo-Asp-Pro specifically inhibited fat intake and had near maximal inhibition (50%) at the 0.03 nmol dose. The enterostatin inhibitory effect on fat intake may reside in the cyclo-diketopiperazine molecule, cyclo-Asp-Pro.

摘要

测试了一系列肠抑素类似物，以研究抑制高脂（HF）饮食摄入活性所需的最小结构。脑室内（ICV）注射肠抑素的剂量反应曲线呈U形（1 nmol时抑制作用最大）。从肠抑素（Val-Pro-Asp-Pro-Arg）中去除或修饰N端缬氨酸会消除活性，C端酰胺化也会如此。三肽（Pro-Asp-Pro）和环二酮哌嗪环-Asp-Pro保留了活性，而线性Asp-Pro二肽则无活性。在适应三选宏量营养素饮食的大鼠中，环-Asp-Pro特异性抑制脂肪摄入，在0.03 nmol剂量时具有接近最大抑制作用（50%）。肠抑素对脂肪摄入的抑制作用可能存在于环二酮哌嗪分子环-Asp-Pro中。