Cromm Philipp M, Spiegel Jochen, Grossmann Tom N
†Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany.
‡Technical University Dortmund, Department of Chemistry and Chemical Biology, Otto-Hahn-Str. 6, 44227 Dortmund, Germany.
ACS Chem Biol. 2015 Jun 19;10(6):1362-75. doi: 10.1021/cb501020r. Epub 2015 Mar 31.
Peptide-based drug discovery has experienced a significant upturn within the past decade since the introduction of chemical modifications and unnatural amino acids has allowed for overcoming some of the drawbacks associated with peptide therapeutics. Strengthened by such features, modified peptides become capable of occupying a niche that emerges between the two major classes of today's therapeutics-small molecules (<500 Da) and biologics (>5000 Da). Stabilized α-helices have proven particularly successful at impairing disease-relevant PPIs previously considered "undruggable." Among those, hydrocarbon stapled α-helical peptides have emerged as a novel class of potential peptide therapeutics. This review provides a comprehensive overview of the development and applications of hydrocarbon stapled peptides discussing the benefits and limitations of this technique.
自引入化学修饰和非天然氨基酸以来，基于肽的药物发现技术在过去十年中取得了显著进展，这些修饰和氨基酸有助于克服与肽疗法相关的一些缺点。基于这些特性，修饰后的肽能够占据当今两类主要疗法——小分子（<500 Da）和生物制剂（>5000 Da）之间的一个细分领域。稳定的α-螺旋已被证明在破坏先前被认为“不可成药”的与疾病相关的蛋白质-蛋白质相互作用（PPI）方面特别成功。其中，烃链稳定的α-螺旋肽已成为一类新型的潜在肽疗法。本文综述了烃链稳定肽的开发和应用，讨论了该技术的优点和局限性。
