McGregor Duncan Patrick
Cyclogenix Limited, Crombie Lodge, Aberdeen Science & Technology Park, Aberdeen, UK.
Curr Opin Pharmacol. 2008 Oct;8(5):616-9. doi: 10.1016/j.coph.2008.06.002. Epub 2008 Jul 16.
Peptides have a number of advantages over small molecules in terms of specificity and affinity for targets, and over antibodies in terms of size. However, sensitivity to serum and tissue proteases coupled with short serum half-life has resulted in few recombinant library derived peptides, making the transition from lead to drug on the market. Recently, a series of technologies have been developed to address both these issues: selection methodologies addressing protease resistance have been developed that when combined with methods such as pegylation antibody Fc attachment and binding to serum albumin look likely to finally turn therapeutic peptides into a widely accepted drug class.
与小分子相比,肽在对靶点的特异性和亲和力方面具有许多优势,与抗体相比在大小方面具有优势。然而,对血清和组织蛋白酶的敏感性以及较短的血清半衰期导致源自重组文库的肽很少,这使得从先导物到上市药物的转变变得困难。最近,已经开发出一系列技术来解决这两个问题:已经开发出解决蛋白酶抗性的筛选方法,当与聚乙二醇化、抗体Fc连接和与血清白蛋白结合等方法结合使用时,有望最终使治疗性肽成为一种被广泛接受的药物类别。