Optimizing Bothropstoxin-I-Derived Peptides: Exploring the Antibacterial Potential of p-BthW.

Autor: Marinho Righetto G; Laboratory of Molecular Epidemiology and Microbiology, Department of Physics and Interdisciplinary Science, University of Sao Paulo, 13563-120 São Carlos, Brazil., Alves Santos-Filho N; Department of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University, 14800-060 Araraquara, Brazil., Oliveira Catarin Nunes L; Department of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University, 14800-060 Araraquara, Brazil., André C; Infectious Disease Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts 02115, United States., Souza JM; Laboratory of Medicinal and Computational Chemistry, Department of Physics and Interdisciplinary Science, University of Sao Paulo, 13563-120 São Carlos, Brazil., Andricopulo AD; Laboratory of Medicinal and Computational Chemistry, Department of Physics and Interdisciplinary Science, University of Sao Paulo, 13563-120 São Carlos, Brazil., Martins Bispo PJ; Infectious Disease Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts 02115, United States., Cilli EM; Department of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University, 14800-060 Araraquara, Brazil., Camargo ILBDC; Laboratory of Molecular Epidemiology and Microbiology, Department of Physics and Interdisciplinary Science, University of Sao Paulo, 13563-120 São Carlos, Brazil.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2024 May 22; Vol. 9 (22), pp. 23662-23674. Date of Electronic Publication: 2024 May 22 (Print Publication: 2024).
DOI: 10.1021/acsomega.4c01303
Abstrakt: Antimicrobial peptides are an emerging class of antibiotics that present a series of advantageous characteristics such as wide structural variety, broad spectrum of activity, and low propensity to select for resistance. They are found in all classes of life as defense molecules. A group of peptides derived from the protein Bothropstoxin-I has been previously studied as an alternative treatment against multi-drug-resistant bacteria. The peptide p-BthTX-I (sequence: KKYRYHLKPFCKK) and its homodimer, linked by disulfide oxidation through the residues of Cys11 and the serum degradation product [sequence: (KKYRYHLKPFC) 2 ], were evaluated and showed similar antimicrobial activity. In this study, we synthesized an analogue of p-BthTX-I that uses the strategy of Fmoc-Lys(Fmoc)-OH in the C-terminal region for dimerization and tryptophan for all aromatic amino acids to provide better membrane interactions. This analogue, named p-BthW, displayed potent antibacterial activity at lower concentrations and maintained the same hemolytic levels as the original molecule. Our assessment revealed that p-BthW has a quick in vitro bactericidal action and prolonged post-antibiotic effect, comparable to the action of polymyxin B. The mode of action of p-BthW seems to rely not only on membrane depolarization but also on necrosis-like effects, especially in Gram-negative bacteria. Overall, the remarkable results regarding the propensity to develop resistance reaffirmed the great potential of the developed molecule.
Competing Interests: The authors declare no competing financial interest.
(© 2024 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE
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