Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold

Biomolecules

Maha AlKhazindar¹  Sherif Elnagdy¹  Keykavous Parang²  Eman H. M. Mohammed²  Shaima A. El-Mowafi²  Wojciech M. Wolf³  Joanna Bojarska³  Zyta M. Ziora⁴  Istvan Toth⁴  Adam Mieczkowski⁵  Ahmed O. Shalash⁶  Mariusz Skwarczynski⁶ 

[1] Botany Department, Faculty of Science, Cairo University, Giza 12613, Egypt;Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Harry and Diane Rinker Health Science Campus, School of Pharmacy, Chapman University, Irvine, CA 92618, USA;Faculty of Chemistry, Institute of General & Inorganic Chemistry, Technical University of Lodz, 90-924 Lodz, Poland;Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia;Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland;School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia;

关键词: cyclic dipeptides;    diketopiperazines;    proline-based DKPs;    drug discovery;    privileged scaffold;    supramolecular structuring;   

DOI  :  10.3390/biom11101515

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown