Triazole-Modified Peptidomimetics: An Opportunity for Drug Discovery and Development

Abstract

Peptidomimetics play a fundamental role in drug design due to their preferential properties regarding natural peptides. In particular, compounds possessing nitrogen-containing heterocycles have been intensively studied in recent years. The triazolyl moiety incorporation decreases the molecule susceptibility to enzymatic degradation, reduction, hydrolysis, and oxidation. In fact, peptides containing triazole rings are a typical example of peptidomimetics. They have all the advantages over classic peptides. Both efficient synthetic methods and biological activity make these systems an interesting and promising object of research. Peptide triazole derivatives display a diversity of biological properties and can be obtained via numerous synthetic strategies. In this review, we have highlighted the importance of the triazole-modified peptidomimetics in the field of drug design. We present an overview on new achievements in triazolyl-containing peptidomimetics synthesis and their biological activity as inhibitors of enzymes or against cancer, viruses, bacteria, or fungi. The relevance of above-mentioned compounds was confirmed by their comparison with unmodified peptides.

Peptidomimetics: An Overview of Recent Medicinal Chemistry Efforts toward the Discovery of Novel Small Molecule Inhibitors

“…Moreover, the amide bond is often replaced by a wide range of isosteres such as thioamides, alkenes, triazole rings, and hydroxy ethylene and hydroxy ethylamine moieties. Of note, the triazole ring is an attractive bioisostere for its peculiar physicochemical properties offering planarity, a dipole moment, and hydrogen bonding similar to the amide bond . Azapeptides represent another example of amide bond isosteres and are known to mimic the tetrahedral transition state occurring after the peptide cleavage, thus contributing to molecule stability.…”

Peptides and Peptidomimetics as Inhibitors of Enzymes Involved in Fibrillar Collagen Degradation

“…Cyclic analogues of above-mentioned sequences were studied in tandem [70]. Generally speaking, the importance of conformationally constrained peptides was underpinned and investigated for various applications, mainly for drug-design purposes [71][72][73][74][75]. The design of new cyclic collagenase inhibitors was based on the following rules: (1) at least four interacting residues should be present; (2) there should be a bulky, hydrophobic group present in the P 1 position; (3) it is required to incorporate glycine and proline in P 1' and P 2' positions, respectively; (4) P 3' position should be occupied by either linear, basic or apolar side chain residue (lysine or aminocaproic acid, Ahx).…”

Metal-Free Synthesis of N-Heterocycles via Intramolecular Electrochemical C-H Aminations

“…N -heterocycles are key structural units in many drugs, biologically interesting molecules and functional materials ( Kim and Movassaghi, 2009 ; Meng et al, 2021 ; Staśkiewicz et al, 2021 ). Therefore, the development of robust synthetic methods for the construction of N -heterocycles has gained increased attention in academia and industry.…”