Modified low molecular weight cyclic peptides as mimetics of BDNF with improved potency, proteolytic stability and transmembrane passage in vitro

被引：31

作者：

Fletcher, Jordan M. ^{[1
]}

Hughes, Richard A. ^{[1
]}

机构：

[1] Univ Melbourne, Dept Pharmacol, Melbourne, Vic 3010, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 07期

关键词：

BDNF; Neurotrophin; Agonist; Antagonist; Neurotrophic factor; p75; APPARENT DRUG PERMEABILITY; THEORETICAL PREDICTIONS; BIOLOGICAL-ACTIVITIES; NEUROTROPHIC FACTORS; CACO-2; MONOLAYERS; FATTY-ACIDS; BLOOD-BRAIN; CELL-LINE; ABSORPTION; TRANSPORT;

D O I：

10.1016/j.bmc.2009.02.053

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We recently reported the development of the BDNF mimetic peptide cyclo-[dPAKKR] 1 which promotes the survival of cultured sensory neurons via a trkB independent mechanism [Fletcher, J. M.; Morton, C. M.; Zwar, R. A.; Murray, S. S.; O'Leary, P. D.; Hughes, R. A. J. Biol. Chem. 2008, 283, 33375]. In the present study we prepared a series of hydrophobically-modified analogues of 1 with an eye to improving its pharmacokinetic properties. Select members of this second generation of compounds showed improved biological activity, stability in plasma, and an ability to cross model biological membranes. Crown Copyright (c) 2009 Published by Elsevier Ltd. All rights reserved.

引用

页码：2695 / 2702

页数：8

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