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Updated: May 1, 2026

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
In silico and in vitro characterization of the antibacterial effects of two novel synthetic peptides derived from
Raiça Dominique Mariana Gomes da Costa Braz1, Rita de Kássia Oliveira da Costa1, Igor Rafael Resende de Oliveira2
1Laboratory of Biomolecule Biotechnology (LBB), Department of Biochemistry, Center of Biosciences (CB), Federal University of Rio Grande do Norte (UFRN), Av. Senador Salgado Filho, 3000, Lagoa Nova, Natal 59072-970, Brazil; Graduate Program in Pharmaceutical Sciences, Federal University of Rio Grande do Norte (UFRN), Rua Gustavo Cordeiro de Farias, S/N, Petropolis, Natal 59012-570, Brazil.
Abstract:
Optimization of naturally occurring antimicrobial peptides (AMPs) seeks synthetic molecules that retain the positive characteristics of their native AMPs while presenting improved features. TsAP-2 is an AMP found in the venom gland of Tityus spp. scorpions, active against Gram-positive bacteria and Candida spp. yeasts. The analogs TsAP-A16 and TsAP-41 were designed by replacing neutral amino acids in TsAP-2 with positively charged ones, aiming to obtain peptides with broader action spectrum. In silico and in vitro methods employed in the characterization of the antibacterial activity of TsAP-A16 and TsAP-A41 revealed greater affinity for bacterial membranes than their native AMP, as well as bactericidal and antibiofilm action of both analogs against Gram-positive and Gram-negative strains. Associations with conventional antibiotics revealed synergistic and additive effects in individual combinations of TsAP-A16 and TsAP-A41 with gentamicin, penicillin and ceftazidime. Considering the accepted mechanism of action of AMPs relies on interactions with cell membranes, associations of AMPs with antimicrobial agents with intracellular targets demonstrates potential for rejuvenating widely-known drugs that have seen a decreased effectiveness due to antimicrobial resistance.
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