Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold
Joanna Bojarska,
Adam Mieczkowski,
Zyta M. Ziora,
Mariusz Skwarczynski,
Istvan Toth,
Ahmed O. Shalash,
Keykavous Parang,
Shaima A. El-Mowafi,
Eman H. M. Mohammed,
Sherif Elnagdy,
Maha AlKhazindar,
Wojciech M. Wolf
Affiliations
Joanna Bojarska
Faculty of Chemistry, Institute of General & Inorganic Chemistry, Technical University of Lodz, 90-924 Lodz, Poland
Adam Mieczkowski
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland
Zyta M. Ziora
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia
Mariusz Skwarczynski
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Istvan Toth
Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia
Ahmed O. Shalash
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Keykavous Parang
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
Shaima A. El-Mowafi
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
Eman H. M. Mohammed
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
Sherif Elnagdy
Botany Department, Faculty of Science, Cairo University, Giza 12613, Egypt
Maha AlKhazindar
Botany Department, Faculty of Science, Cairo University, Giza 12613, Egypt
Wojciech M. Wolf
Faculty of Chemistry, Institute of General & Inorganic Chemistry, Technical University of Lodz, 90-924 Lodz, Poland
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.
