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.

Keywords: 1,2,3-triazole; 1,2,4-triazole; CuAAC; antibacterial triazoles; antifungal triazoles; antiviral triazoles; disulphide bond mimetic; enzyme inhibitors.

Figure 1

Structures of the two isomeric forms of triazoles. (A) 1,2,3-triazole; (B) 1,2,4-triazole (Souza and Miranda, 2019).

Figure 2

Methods to prepare the triazoles from α-diazoimines (Jordão et al., 2011).

Figure 3

The Huisgen cycloaddition. (A) Under thermal conditions and (B) catalysed by Cu(I) ions.

Figure 4

Synthetic strategies of triazolyl containing cyclopeptidomimetics. (A) CuAAC in solution-phase peptide synthesis; (B) incorporation of triazole during SPPS; (C) attachment of triazole to the solid support by CuAAC; (D) conjugation of peptide fragment after CuAAC in solution (Valverde and Mindt, 2012).

Figure 5

The glycotriazole-peptide derivatives (Junior et al., 2017).

Figure 6

The cyclic peptidomimetic of Smac (structure 2: R = phenyl; structure 3: R = benzyl) (Sun et al., 2010).

Figure 7

The peptidomimetic active against lung cancer cells, including a triazole moiety (Tahoori et al., 2014).