Synthetic peptide derived from Scorpion venom displays minimal toxicity and anti-infective activity in an animal model
Appears in Collections:
Multidrug-resistant bacteria represent a global health problem increasingly leading to infections that are untreatable with our existing antibiotic arsenal. Therefore, it is critical to identify novel effective antimicrobials. Venoms represent an underexplored source of potential antibiotic molecules. Here, we engineered a peptide (IsCT1-NH2) derived from the venom of the scorpion Opisthacanthus madagascariensis, whose application as an antimicrobial had been traditionally hindered by its high toxicity. Through peptide design and the knowledge obtained in preliminary studies with single and double-substituted analogs, we engineered IsCT1 derivatives with multiple amino acid substitutions to assess the impact of net charge on antimicrobial activity and toxicity. We demonstrate that increased net charge (from +3 to +6) significantly reduced toxicity toward human erythrocytes. Our lead synthetic peptide, [A]1[K]3[F]5[K]8-IsCT1-NH2 (net charge of +4), exhibited increased antimicrobial activity against Gram-negative and Gram-positive bacteria in vitro and enhanced anti-infective activity in a mouse model. Mechanism of action studies revealed that the increased antimicrobial activity of our lead molecule was due, at least in part, to its enhanced ability to permeabilize the outer membrane and depolarize the cytoplasmic membrane. In summary, we describe a simple method based on net charge tuning to turn highly toxic venom-derived peptides into viable therapeutics.
Oliveira CS, Torres MDT, Pedron CN, Andrade VB, Silva Junior PI, Silva FD, et al. Synthetic peptide derived from Scorpion venom displays minimal toxicity and anti-infective activity in an animal model. ACS Infect Dis. 2021 Aug;9(7):2736–2745. doi:10.1021/acsinfecdis.1c00261.
Link to cite this reference
(CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ; (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo ; (UFABC) Universidade Federal do ABC ; University of Pennsylvania ; (NIH) National Institutes of Health ; (DTRA) Defense Threat Reduction Agency ; (IDOM) Institute for Diabetes, Obesity, and Metabolism
The access to the publications deposited in this repository respects the licenses from journals and publishers.