Institute of Biochemistry, Faculty of Biosciences, Pharmacy & Psychology, Universität Leipzig, Brüderstrasse 34, 04103 Leipzig, Germany.
Future Med Chem. 2012 Aug;4(12):1567-86. doi: 10.4155/fmc.12.76.
The main benefit of natural peptides, peptide analogs and newly designed peptides as therapeutics, lies in their high selectivity and affinity, which are frequently in the nanomolar range. New drugs targeting protein-protein interactions often require larger interaction sites than small molecules can offer. Thus, many peptidic drugs are already applied in therapy at the current state. The next generation of peptide-based therapeutic agents is currently on its way from basic research to clinical studies and eventually to the pharmaceutical market. Development of more robust and long-lasting drugs owing to well-known and new stabilization strategies is yielding novel and continuously improving peptide drugs. The introduction of smart linkers that exhibit stability towards blood plasma but intracellular lability will lead to target-oriented activity, which might successfully decrease side effects. In this review, peptidic therapeutics on the market, in clinical studies and some of those in basic research are characterized. Stabilization strategies and intelligent linkers are discussed with respect to their use in peptide drug therapy.
天然肽、肽类似物和新设计的肽作为治疗剂的主要优势在于它们的高选择性和亲和力，通常在纳摩尔范围内。针对蛋白质-蛋白质相互作用的新药通常需要比小分子更大的相互作用位点。因此，许多肽类药物已经在目前的治疗中得到应用。基于肽的治疗药物的下一代目前正在从基础研究到临床研究，最终进入药物市场的路上。由于采用了众所周知的和新的稳定化策略，开发更强大和更持久的药物正在产生新的、不断改进的肽类药物。引入对血浆稳定但细胞内不稳定的智能连接子将导致靶向活性，这可能成功降低副作用。在这篇综述中，对市场上、临床研究中和基础研究中的一些肽类治疗药物进行了描述。讨论了稳定化策略和智能连接子在肽类药物治疗中的应用。
