Beeley NR
Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, CA 92121, USA.
Drug Discov Today. 2000 Aug;5(8):354-363. doi: 10.1016/s1359-6446(00)01528-2.
The biological activity of peptides is of enormous interest to the pharmaceutical industry, but endogenous peptides themselves typically have some limitations regarding bioavailability and oral activity. Peptide mimicry by design used to be touted as a solution to these problems and was focused on impersonating secondary structural motifs, particularly beta-turns, but this approach has yielded few pharmaceutical products. Today, the process of identifying and optimizing peptide mimics is driven mainly by screening to obtain hits, followed by optimization, which might include design based on arranging pharmacophores appropriately in three dimensions. A consequence of this is that one of the more difficult problems in drug discovery, namely the identification of non-peptide agonists at peptide receptors, is beginning to be solved.
肽的生物活性引起了制药行业的极大兴趣，但内源性肽本身在生物利用度和口服活性方面通常存在一些局限性。过去，通过设计进行肽模拟被吹捧为解决这些问题的方法，并且重点是模仿二级结构基序，特别是β-转角，但这种方法产生的药品很少。如今，识别和优化肽模拟物的过程主要由筛选以获得命中物驱动，随后进行优化，这可能包括基于在三维空间中适当地排列药效基团的设计。由此产生的一个结果是，药物发现中较困难的问题之一，即肽受体上非肽激动剂的识别，开始得到解决。
