Molecular hybridization strategy for tuning bioactive peptide function.

Autor: Pedron CN; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, 09210580, Brazil.; Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, 04044020, Brazil., Torres MT; Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.; Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA, USA., Oliveira CS; Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, 04044020, Brazil., Silva AF; Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, 04044020, Brazil., Andrade GP; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, 09210580, Brazil.; Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, 04044020, Brazil., Wang Y; Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.; Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA, USA., Pinhal MAS; Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, 04044020, Brazil., Cerchiaro G; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, 09210580, Brazil., da Silva Junior PI; Laboratório de Toxinologia Aplicada (LETA) - Instituto Butantan, São Paulo, SP, 05503900, Brazil., da Silva FD; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, 09210580, Brazil., Radhakrishnan R; Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.; Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA, USA., de la Fuente-Nunez C; Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. cfuente@upenn.edu.; Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA. cfuente@upenn.edu.; Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA, USA. cfuente@upenn.edu., Oliveira Junior VX; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, 09210580, Brazil. vani.junior@ufabc.edu.br.; Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, 04044020, Brazil. vani.junior@ufabc.edu.br.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Oct 19; Vol. 6 (1), pp. 1067. Date of Electronic Publication: 2023 Oct 19.
DOI: 10.1038/s42003-023-05254-7
Abstrakt: The physicochemical and structural properties of antimicrobial peptides (AMPs) determine their mechanism of action and biological function. However, the development of AMPs as therapeutic drugs has been traditionally limited by their toxicity for human cells. Tuning the physicochemical properties of such molecules may abolish toxicity and yield synthetic molecules displaying optimal safety profiles and enhanced antimicrobial activity. Here, natural peptides were modified to improve their activity by the hybridization of sequences from two different active peptide sequences. Hybrid AMPs (hAMPs) were generated by combining the amphipathic faces of the highly toxic peptide VmCT1, derived from scorpion venom, with parts of four other naturally occurring peptides having high antimicrobial activity and low toxicity against human cells. This strategy led to the design of seven synthetic bioactive variants, all of which preserved their structure and presented increased antimicrobial activity (3.1-128 μmol L -1 ). Five of the peptides (three being hAMPs) presented high antiplasmodial at 0.8 μmol L -1 , and virtually no undesired toxic effects against red blood cells. In sum, we demonstrate that peptide hybridization is an effective strategy for redirecting biological activity to generate novel bioactive molecules with desired properties.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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