کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1370042 981807 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Peptide-based inhibitors of protein–protein interactions
ترجمه فارسی عنوان
مهارکننده های پپتیدی برهمکنش پروتئین
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی

Protein–protein interactions (PPIs) are key elements of several important biological processes and have emerged as valuable targets in medicinal chemistry. Importantly, numerous specific protein–protein interactions (e.g., p53–HDM2 and Bcl-2–BH3 domains) were found to be involved in the development of several diseases, including various types of cancer. In general, the discovery of new synthetic PPI inhibitors is a challenging task because protein surfaces have not evolved in a manner that allows for specific binding of low molecular weight compounds.Here, we review the discovery strategies for peptide-based PPI inhibitors. Although peptide-based drug candidates exhibit significant drawbacks (in particular, low proteolytic stability), modifications of either the side chains or backbone could provide molecules of interest. Moreover, due to the large molecular size of peptide-based compounds, the discovery of molecules that specifically interact with extended protein surfaces is possible. Two major strategies for constructing peptide-based PPI inhibitors are as follows: (a) cyclization (e.g., stapled peptides) and (b) modification of the backbone structure (e.g., β-peptides and peptoids). These approaches for constructing PPI inhibitors enhance both the inhibitory activity and pharmacokinetic properties compared with non-modified α-peptides.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 26, Issue 3, 1 February 2016, Pages 707–713
نویسندگان
, ,