Peleshok J, Saragovi H U
Lady Davis Institute-Jewish General Hospital, 3755 Cote St. Catherine, F-223, Montreal, QC, Canada H3T 1E2.
Biochem Soc Trans. 2006 Aug;34(Pt 4):612-7. doi: 10.1042/BST0340612.
Neurotrophins regulate cell survival, death, differentiation and growth. Neurotrophins and their receptors have been validated for pathologies including neurodegenerative disorders of the central nervous system and the peripheral nervous system, certain types of cancers, asthma, inflammation and others. Development of neurotrophin-based therapeutics is important due to the limitations of using whole neurotrophins as pharmacological agents. The use of mimicry has proven to be an alternative. Mimetics can be developed through a number of different approaches. To develop receptor-binding agents, we have used anti-receptor antibody mimicry and neurotrophin mimicry. To develop ligand-binding agents, we have used antiligand antibody mimicry and receptor mimicry. High-throughput screening can be incorporated to complement any of these approaches. The end result is small molecule peptidomimetics with properties favourable over proteins. The present review will offer a general overview of these strategies with a few proven examples from our laboratory.
神经营养因子调节细胞存活、死亡、分化和生长。神经营养因子及其受体已被证实与多种病症相关,包括中枢神经系统和周围神经系统的神经退行性疾病、某些类型的癌症、哮喘、炎症等。由于将完整的神经营养因子用作药物存在局限性,基于神经营养因子的疗法的开发具有重要意义。事实证明,使用模拟物是一种替代方法。模拟物可以通过多种不同的方法来开发。为了开发受体结合剂,我们使用了抗受体抗体模拟和神经营养因子模拟。为了开发配体结合剂,我们使用了抗配体抗体模拟和受体模拟。高通量筛选可以与这些方法中的任何一种相结合。最终结果是具有优于蛋白质特性的小分子肽模拟物。本综述将概述这些策略,并列举我们实验室的一些已证实的实例。