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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

IsCT-based analogs intending better biological activity

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Author(s):
Chica Acevedo, Isabel Cristina [1] ; Silva, Jr., Pedro Ismael [2] ; Silva, Fernanda Dias [1] ; Araujo, Iris [1] ; Alves, Flavio Lopes [3, 1] ; Oliveira, Cyntia Silva [3] ; Oliveira, Jr., Vani Xavier [3, 1]
Total Authors: 7
Affiliation:
[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil
[2] Inst Butantan, Lab Especial Toxinol Aplicada, Sao Paulo, SP - Brazil
[3] Univ Fed Sao Paulo, Dept Biofis, Sao Paulo, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF PEPTIDE SCIENCE; OCT 2019.
Web of Science Citations: 0
Abstract

IsCT1-NH2 is a cationic antimicrobial peptide isolated from the venom of the scorpion Opisthacanthus madagascariensis that has a tendency to form an alpha-helical structure and shows potent antimicrobial activity and also inopportunely shows hemolytic effects. In this study, five IsCT1 (ILGKIWEGIKSLF)-based analogs with amino acid modifications at positions 1, 3, 5, or 8 and one analog with three simultaneous substitutions at the 1, 5, and 8 positions were designed. The net charge of each analog was between +2 and +3. The peptides obtained were characterized by mass spectrometry and analyzed by circular dichroism for their structure in different media. Studies of antimicrobial activity, hemolytic activity, and stability against proteases were also carried out. Peptides with a substitution at position 3 or 5 ({[}L](3)-IsCT1-NH2, {[}K](3)-IsCT1-NH2, or {[}F](5)-IsCT1-NH2) showed no significant change in an activity relative to IsCT1-NH2. The addition of a proline residue at position 8 ({[}P](8)-IsCT1-NH2) reduced the hemolytic activity as well as the antimicrobial activity (MIC ranging 3.13-50 mu mol L-1), and the addition of a tryptophan residue at position 1 ({[}W](1)-IsCT1-NH2) increased the hemolytic activity (MHC = 1.56 mu mol L-1) without an improvement in antimicrobial activity. The analog {[}A](1){[}F](5){[}K](8)-IsCT1-NH2, which carries three simultaneous modifications, presented increasing or equivalent values in antimicrobial activity (MIC approximately 0.38 and 12.5 mu mol L-1) with a reduction in hemolytic activity. In addition, this analog presented the best resistance against proteases. This kind of strategy can find functional hotspots in peptide molecules in an attempt to generate novel potent peptide antibiotics. (AU)

FAPESP's process: 17/03046-2 - Biologically active peptides against pathogenic microorganisms and cancer cells
Grantee:Vani Xavier de Oliveira Junior
Support type: Regular Research Grants
FAPESP's process: 14/12938-6 - Biologically active peptides against pathogenic micro-organisms
Grantee:Vani Xavier de Oliveira Junior
Support type: Regular Research Grants