School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute and Curtin Institute for Computation, Curtin University, GPO Box U1987, Perth WA 6845, Australia.
Molecules. 2018 Jul 16;23(7):1733. doi: 10.3390/molecules23071733.
This review summarises the current knowledge of Gomesin (Gm), an 18-residue long, cationic anti-microbial peptide originally isolated from the haemocytes of the Brazilian tarantula The peptide shows potent cytotoxic activity against clinically relevant microbes including Gram-positive and Gram-negative bacteria, fungi, and parasites. In addition, Gm shows in-vitro and in-vivo anti-cancer activities against several human and murine cancers. The peptide exerts its cytotoxic activity by permeabilising cell membranes, but the underlying molecular mechanism of action is still unclear. Due to its potential as a therapeutic agent, the structure and membrane-binding properties, as well as the leakage and cytotoxic activities of Gm have been studied using a range of techniques. This review provides a summary of these studies, with a particular focus on biophysical characterisation studies of peptide variants that have attempted to establish a structure-activity relationship. Future studies are still needed to rationalise the binding affinity and cell-type-specific selectivity of Gm and its variants, while more pre-clinical studies are required to develop Gm into a therapeutically useful peptide.
本文综述了 Gomesin（Gm）的现有知识，Gm 是一种 18 个氨基酸组成的阳离子抗菌肽，最初从巴西狼蛛的血细胞中分离得到。该肽对临床相关微生物具有强大的细胞毒性活性，包括革兰氏阳性和革兰氏阴性细菌、真菌和寄生虫。此外，Gm 对几种人和鼠类癌症具有体外和体内的抗癌活性。该肽通过破坏细胞膜发挥细胞毒性作用，但作用的潜在分子机制尚不清楚。由于其作为治疗剂的潜力，已经使用多种技术研究了 Gm 的结构和膜结合特性以及泄漏和细胞毒性活性。本文综述了这些研究，特别关注了试图建立构效关系的肽变体的生物物理特性研究。仍需要进一步的研究来合理化 Gm 及其变体的结合亲和力和细胞类型特异性选择性，同时需要更多的临床前研究将 Gm 开发成一种治疗上有用的肽。
