Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Curr Pharm Biotechnol. 2011 Aug;12(8):1101-16. doi: 10.2174/138920111796117300.
Peptides have emerged as important therapeutics that are being rigorously tested in angiogenesis-dependent diseases due to their low toxicity and high specificity. Since the discovery of endogenous proteins and protein fragments that inhibit microvessel formation (thrombospondin, endostatin) several peptides have shown promise in pre-clinical and clinical studies for cancer. Peptides have been derived from thrombospondin, collagens, chemokines, coagulation cascade proteins, growth factors, and other classes of proteins and target different receptors. Here we survey recent developments for anti-angiogenic peptides with length not exceeding 50 amino acid residues that have shown activity in pre-clinical models of cancer or have been tested in clinical trials; some of the peptides have been modified and optimized, e.g., through L-to-D and non-natural amino acid substitutions. We highlight technological advances in peptide discovery and optimization including computational and bioinformatics tools and novel experimental techniques.
肽类药物已成为治疗学中的重要研究方向，由于其低毒性和高特异性，在血管生成依赖性疾病的治疗中得到了严格的测试。自发现可抑制微血管形成的内源性蛋白和蛋白片段（如血栓反应蛋白、内皮抑素）以来，已有多种肽类药物在癌症的临床前和临床研究中显示出良好的应用前景。这些肽类药物来源于血栓反应蛋白、胶原蛋白、趋化因子、凝血级联蛋白、生长因子和其他蛋白类别，并针对不同的受体。本文综述了近年来长度不超过 50 个氨基酸残基的抗血管生成肽的最新研究进展，这些肽类药物在癌症的临床前模型中具有活性，或已在临床试验中进行了测试；其中一些肽类药物已经经过修饰和优化，例如通过 L 到 D 氨基酸的取代和非天然氨基酸的取代。本文重点介绍了肽类药物发现和优化方面的技术进展，包括计算和生物信息学工具以及新的实验技术。
