The Wheel of Fortune: Helical Wheel Alanine Scanning of a Spider Venom Antimicrobial Peptide Reveals Residues Involved in Antimicrobial and Cytotoxic Activity.

Autor: Fernando JC; Institute of Chemistry, College of Science, University of the Philippines Diliman, Quezon City, Metro Manila, Philippines., Batucan JD; Marine Science Institute, College of Science, University of the Philippines Diliman, Quezon City, Metro Manila, Philippines., Peran JE; Marine Science Institute, College of Science, University of the Philippines Diliman, Quezon City, Metro Manila, Philippines., Salvador-Reyes LA; Marine Science Institute, College of Science, University of the Philippines Diliman, Quezon City, Metro Manila, Philippines., Villaraza AJL; Institute of Chemistry, College of Science, University of the Philippines Diliman, Quezon City, Metro Manila, Philippines.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2024 Dec 02; Vol. 19 (23), pp. e202400488. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1002/cmdc.202400488
Abstrakt: A preference for several amino acids is observed to occur at particular positions of cationic α-helical antimicrobial peptides (AMPs), which ensures the formation of amphipathic regions once they assume their correct secondary structure in membranes or membrane-mimicking environments and makes them active against pathogens. This study determined the effect of alanine mutations on the secondary structure and bioactivity of lyp1987 (GRLQAFLAKMKEIAAQTL-NH 2 ), a cationic α-helical AMP obtained from the venom of Lycosa poonaensis which exhibits broad range activity against Gram-positive and Gram-negative bacteria with micromolar minimum inhibitory concentrations (MIC). CD spectroscopy revealed no significant difference in the secondary structure, with all alanine-substituted analogs exhibiting predominantly α-helical structure in buffered 2,2,2-trifluoroethanol solution. Alanine substitution at Glu12 and Thr17 increased the activity of lyp1987 against Gram-positive and -negative bacteria, while alanine substitution at Lys9 increased its selectivity against Gram-positive bacteria. Further investigation can be done to determine positions and substitutions that will give less cytotoxic analogs.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: