Northfield Susan E, Wang Conan K, Schroeder Christina I, Durek Thomas, Kan Meng-Wei, Swedberg Joakim E, Craik David J
The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia.
The University of Queensland, Institute for Molecular Bioscience, Brisbane 4072, QLD, Australia.
Eur J Med Chem. 2014 Apr 22;77:248-57. doi: 10.1016/j.ejmech.2014.03.011. Epub 2014 Mar 6.
Recently disulfide-rich head-to-tail cyclic peptides have attracted the interest of medicinal chemists owing to their exceptional thermal, chemical and enzymatic stability brought about by their constrained structures. Here we review current trends in the field of peptide-based pharmaceuticals and describe naturally occurring cyclic disulfide-rich peptide scaffolds, discussing their pharmaceutically attractive properties and benefits. We describe how we can utilise these stable frameworks to graft and/or engineer pharmaceutically interesting epitopes to increase their selectivity and bioactivity, opening up new possibilities for addressing 'difficult' pharmaceutical targets.
最近，富含二硫键的头对尾环肽因其受限结构所带来的卓越热稳定性、化学稳定性和酶稳定性而引起了药物化学家的关注。在此，我们综述了基于肽的药物领域的当前趋势，并描述了天然存在的富含二硫键的环肽支架，讨论了它们在药学上具有吸引力的特性和优势。我们描述了如何利用这些稳定的框架来嫁接和/或设计具有药学意义的表位，以提高其选择性和生物活性，为攻克“难成药”靶点开辟新的可能性。
