Novel Peptide-Triazole Conjugates: Strategic Synthesis, Antimicrobial Properties, and Molecular Docking Study

The rising incidence of multidrug-resistant (MDR) bacteria demands the creation of innovative antimicrobial agents characterized by enhanced stability and efficacy. In this study, a series of peptide-heterocycle conjugates was systematically designed and synthesized using solid-phase peptide synthesis (SPPS), featuring octapeptide-triazole conjugates modified with a triazole-based moiety. Non-proteinogenic amino acids, specifically 2-aminoisobutyric acid (Aib) and 2-naphthylalanine (2-Nal), were used to add structural diversity. SPPS is a relatively easy way to synthesize these compounds, which ensures accuracy in the sequence. The synthesized peptides were subjected to an antimicrobial activity assessment following a molecular docking study. In comparison to the standard drug, compound 7e exhibited promising antibacterial activity against E. coli, with the MIC value of 12 μg/mL, whereas compound 7a showed enhanced activity against P. aeruginosa with the MIC value of 12 μg/mL. Compound 7a exhibited better to moderate antifungal activity against C. albicans, with the MIC values of 25 μg/mL.