Ullah Aaqib, Shaheen Farzana, Salar Uzma, Tzakos Andreas G, Gerothanassis Ioannis P
Third World Center for Science and Technology, H.E.J Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece.
J Pept Sci. 2025 Sep;31(9):e70045. doi: 10.1002/psc.70045.
Marine sponges are sessile invertebrates found in moderate, arctic, and tropical regions, serving as a valuable reservoir of bioactive compounds, particularly Pro-rich peptides. Among these, cyclic peptides have attracted significant interest due to their diverse therapeutic properties. One notable example is Stylissatin A (SA), a Pro-rich cyclic peptide reported from the marine sponge Stylissa massa. SA and its analogues have shown promising biological activities, including anti-inflammatory, anticancer, and anti-obesity effects. Despite the vast potential of marine-derived peptides, only a small number have progressed to the pharmaceutical market. Cyclic peptides like SA offer unique opportunities for molecular modifications and total synthesis, enabling the enhancement of potency, improvement of physicochemical properties, and optimization of synthetic yields. This review highlights the synthetic strategies developed for the total synthesis of SA, explores its structural features and related analogues, and discusses their therapeutic potential, underscoring the promise of SA-based scaffolds as novel peptide-based drug candidates.
海洋海绵是一种固着性无脊椎动物，分布于温带、北极和热带地区，是生物活性化合物，特别是富含脯氨酸的肽的宝贵来源。其中，环肽因其多样的治疗特性而备受关注。一个显著的例子是Stylissatin A（SA），一种从海洋海绵Stylissa massa中分离出的富含脯氨酸的环肽。SA及其类似物已显示出有前景的生物活性，包括抗炎、抗癌和抗肥胖作用。尽管海洋来源的肽具有巨大潜力，但只有少数进入了制药市场。像SA这样的环肽为分子修饰和全合成提供了独特的机会，能够增强效力、改善物理化学性质并优化合成产率。本文综述了为SA的全合成开发的合成策略，探讨了其结构特征和相关类似物，并讨论了它们的治疗潜力，强调了基于SA的支架作为新型肽类药物候选物的前景。
