College of Sciences, Shanghai University, Shanghai, China.
Institute of Translational Medicine, Shanghai University, Shanghai, China.
J Pept Sci. 2022 Jul;28(7):e3401. doi: 10.1002/psc.3401. Epub 2022 Feb 1.
Alyteserin-2a (ILGKLLSTAAGLLSNLNH ) is isolated from the skin exudates of midwife toad and has a wide range of biological applications. However, the use of alyteserin-2a as an antitumor agent is limited due to its structural flexibility. In this study, a series of stapled peptides were prepared through hydrocarbon stapling modification without destroying the key residues, and their chemical and biological properties were further evaluated for enhancing the application potential of alyteserin-2a in the field of antitumor drugs development. Among them, alyteserin-2a-Sp3 displayed significant improvement in helicity levels, protease resistance, and antitumor activity compared to that of the template peptide alyteserin-2a, indicating that alyteserin-2a-Sp3 had a potential to become a lead compound for the development of novel antitumor drugs. This study confirms the important effect of hydrocarbon stapling strategy on the secondary structure, hydrolase stability, and biological activity of alyteserin-2a.
阿利特林-2a（ILGKLLSTAAGLLSNL-NH）是从中度助产蟾蜍的皮肤分泌物中分离出来的，具有广泛的生物学应用。然而，由于其结构的灵活性，阿利特林-2a 的抗肿瘤应用受到限制。在这项研究中，通过烃 stapling 修饰制备了一系列订书肽，在不破坏关键残基的情况下进一步评估了它们的化学和生物学性质，以提高阿利特林-2a 在抗肿瘤药物开发领域的应用潜力。其中，阿利特林-2a-Sp3 与模板肽阿利特林-2a 相比，显示出显著提高的螺旋水平、蛋白酶抗性和抗肿瘤活性，表明阿利特林-2a-Sp3 有潜力成为开发新型抗肿瘤药物的先导化合物。这项研究证实了烃 stapling 策略对阿利特林-2a 的二级结构、水解酶稳定性和生物学活性的重要影响。
