Bailly Christian
UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, CHU Lille, CNRS, Inserm, OncoLille Institute, University of Lille, 59000 Lille, France.
Institute of Pharmaceutical Chemistry Albert Lespagnol (ICPAL), Faculty of Pharmacy, University of Lille, 59006 Lille, France.
Mar Drugs. 2025 Oct 9;23(10):397. doi: 10.3390/md23100397.
Diketopiperazines (DKPs) are biologically important cyclic dipeptides widespread in nature, associated primarily with microorganisms. This is the case for the 2,5-DKP derivative cyclo(L-Leu-L-Pro) (cLP), also known as gancidin W or PPDHMP, identified from a variety of bacteria and fungi, and occasionally found in food products. The present review retraces the discovery of cLP, its identification in living species, its chemical syntheses, and its biochemical properties. In bacteria, cLP is often associated with other DKPs to serve as a defense element against other microorganisms and/or as a regulator of bacterial growth. cLP plays a role in quorum-sensing and functions as an anticariogenic and antifungal agent. The antimicrobial mechanism of action and molecular targets of cLP are evoked. The interest in cLP for combatting certain parasitic diseases, such as malaria, and cancers is discussed. The capacity of cLP to interact with CD151 and to down-regulate the expression of this tetraspanin can be exploited to reduce tumor dissemination and metastases. The review sheds light on the pharmacology and specific properties of cyclo(L-Leu-L-Pro), which can be useful for the development of a novel therapeutic approach for different human pathologies. It is also of interest to help define the bioactivity and mechanisms of action of closely related DKP-based natural products.
二酮哌嗪（DKPs）是一类在生物学上具有重要意义的环状二肽，广泛存在于自然界中，主要与微生物相关。从多种细菌和真菌中鉴定出的2,5-DKP衍生物环（L-亮氨酸-L-脯氨酸）（cLP），也称为甘西丁W或PPDHMP，情况就是如此，偶尔也会在食品中发现。本综述追溯了cLP的发现过程、在生物物种中的鉴定、化学合成及其生化特性。在细菌中，cLP常与其他DKPs结合，作为抵御其他微生物的防御元素和/或作为细菌生长的调节剂。cLP在群体感应中发挥作用，并具有抗龋齿和抗真菌的功能。文中探讨了cLP的抗菌作用机制和分子靶点。还讨论了cLP在对抗某些寄生虫病（如疟疾）和癌症方面的潜在应用。cLP与CD151相互作用并下调这种四跨膜蛋白表达的能力可用于减少肿瘤扩散和转移。这篇综述揭示了环（L-亮氨酸-L-脯氨酸）的药理学和特殊性质，这对于开发针对不同人类疾病的新型治疗方法可能是有用的。这也有助于确定基于DKP的密切相关天然产物的生物活性和作用机制。
