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Sep, 2022;54 (9): 1327-1336.

Design and modification of frog skin peptide brevinin-1GHa with enhanced antimicrobial activity on Gram-positive bacterial strains.

Şeyda Kara, Cemil Kürekci, Muharrem Akcan
Author Information
  1. Şeyda Kara: Department of Biochemistry, Faculty of Arts and Sciences, Kütahya Dumlupınar University, 43100, Kütahya, Turkey. ORCID
  2. Cemil Kürekci: Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, Hatay Mustafa Kemal University, 31030, Antakya, Hatay, Turkey. ORCID
  3. Muharrem Akcan: Department of Biochemistry, Faculty of Arts and Sciences, Kütahya Dumlupınar University, 43100, Kütahya, Turkey. muharrem.akcan@dpu.edu.tr. ORCID
PMID: 35852614 DOI: 10.1007/s00726-022-03189-7

Abstract

Naturally occurring frog skin peptides are one of largest sources of antimicrobial peptides that have many advantages including high potency, broad spectrum of targets and low susceptibility to multiple drug-resistance bacteria. However, they also have disadvantages such as hemolytic activity, low stability and high production costs. For these reasons, various strategies have been applied to overcome these drawbacks restricting their use in clinical trials. Previously reported brevinin-1GHa (BR-1GHa) is a 24 amino acid long antimicrobial peptide isolated from Hylarana guentheri with hemolytic activity. To enhance the antimicrobial activity of this peptide and to reduce its hemolytic activity, we designed five new temporin like analogues and examined their bioactivities. Temporins are another class of frog skin peptides without hemolytic activity and shorter than brevinins. When the antimicrobial activities of new analogues were examined against a panel of microorganisms, BR-1GHa-3, in which two alanine residues in the truncated version of BR-1GHa were replaced with leucine, exhibited significantly improved antimicrobial activity against Gram-positive bacterial strains (e.g., S. aureus ATCC 29213 and E. casseliflavus ATCC 700327) with lower hemolytic activity compared to the BR-1GHa peptide. Furthermore, BR-1GHa-4 analogue, in which Gly3 was replaced with Pro, did not show any hemolytic activity except for highest (128 µM) concentration tested and have a strong antimicrobial effect on Gram-positive bacteria (e.g., E. faecalis ATCC 51299 and B. cereus ATCC 13061).

Keywords

Antimicrobial activity Frog skin peptides Hemolytic activity Solid-phase peptide synthesis Structure–activity relationships

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Grants

  1. 2019-18/Dumlupinar Üniversitesi

MeSH Term

Amino Acid Sequence
Amphibian Proteins
Animals
Anti-Bacterial Agents
Anti-Infective Agents
Gram-Positive Bacteria
Hemolysis
Microbial Sensitivity Tests
Ranidae
Skin
Staphylococcus aureus

Chemicals

Amphibian Proteins
Anti-Bacterial Agents
Anti-Infective Agents
Journal Article

Word Cloud

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