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IsCT‐based analogs intending better biological activity
Author(s) -
Acevedo Isabel Cristina Chica,
Silva Jr Pedro Ismael,
Silva Fernanda Dias,
Araújo Iris,
Alves Flávio Lopes,
Oliveira Cyntia Silva,
Oliveira Jr Vani Xavier
Publication year - 2019
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3219
Subject(s) - antimicrobial , chemistry , circular dichroism , stereochemistry , peptide , hemolysis , residue (chemistry) , biological activity , antimicrobial peptides , proteases , biochemistry , enzyme , in vitro , organic chemistry , biology , immunology
IsCT1‐NH 2 is a cationic antimicrobial peptide isolated from the venom of the scorpion Opisthacanthus madagascariensis that has a tendency to form an α‐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‐NH 2 , [K] 3 ‐IsCT1‐NH 2 , or [F] 5 ‐IsCT1‐NH 2 ) showed no significant change in an activity relative to IsCT1‐NH 2 . The addition of a proline residue at position 8 ([P] 8 ‐IsCT1‐NH 2 ) reduced the hemolytic activity as well as the antimicrobial activity (MIC ranging 3.13‐50 μmol L −1 ), and the addition of a tryptophan residue at position 1 ([W] 1 ‐IsCT1‐NH 2 ) increased the hemolytic activity (MHC = 1.56 μmol L −1 ) without an improvement in antimicrobial activity. The analog [A] 1 [F] 5 [K] 8 ‐IsCT1‐NH 2 , which carries three simultaneous modifications, presented increasing or equivalent values in antimicrobial activity (MIC approximately 0.38 and 12.5 μmol 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.