Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold.
Cyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the biological and structural profile of these appealing biomolecules, with a particular emphasis on those with anticancer properties, since cancers are the main cause of death all over the world. Additionally, we provide a consideration on supramolecular structuring and synthons, based on the proline-based DKP privileged scaffold, for inspiration in the design of compound libraries in search of ideal ligands, innovative self-assembled nanomaterials, and bio-functional architectures.
['Bojarska|Joanna|J|0000-0001-9190-6913', 'Mieczkowski|Adam|A|0000-0002-5104-2564', 'Ziora|Zyta M|ZM|0000-0002-9664-3101', 'Skwarczynski|Mariusz|M|0000-0001-7257-807X', 'Toth|Istvan|I|', 'Shalash|Ahmed O|AO|', 'Parang|Keykavous|K|0000-0001-8600-0893', 'El-Mowafi|Shaima A|SA|', 'Mohammed|Eman H M|EHM|', 'Elnagdy|Sherif|S|0000-0003-1331-8977', 'AlKhazindar|Maha|M|0000-0002-3244-9377', 'Wolf|Wojciech M|WM|']
cyclic dipeptides diketopiperazines drug discovery supramolecular structuring proline-based DKPs privileged scaffold