Roles of the Conserved Amino Acid Residues in Reduced Human Defensinâ
5: Cysteine and Arginine Are Indispensable for Its Antibacterial Action and LPS Neutralization.
ChemMedChem
; 14(15): 1457-1465, 2019 08 06.
Article
in En
| MEDLINE
| ID: mdl-31290614
ABSTRACT
Antimicrobial peptides (AMPs) that are able to neutralize toxins are promising antibiotics. In this study we investigated the role of structurally conserved amino acids in reduced human defensinâ
5 (HD5RED ), which is an endogenous peptide with antibacterial action and the ability to neutralize lipopolysaccharide (LPS). Cys residues and high Arg content, rather than Gly18 and Arg6 -Glu14 , were found to be indispensable for HD5RED binding to lipidâ
A, for penetrating the bacterial outer and inner membranes, and for eliminating bacteria. Otherwise, all the conserved sites were requisite for HD5RED to block the interaction between LPS and LPS-binding protein and to suppress the TLR4-NF-κB signaling pathway initiated by LPS. Accordingly, we designed the acetamidomethylated Acm Cys-E21R-HD5RED , which was much more potent than HD5RED at eliminating bacteria and which can neutralize LPS. Acm Cys-E21R-HD5RED was also found to exhibit a synergistic effect with ciprofloxacin in killing multidrug-resistant Acinetobacter baumannii. The results of this study, in which multifunctional AMPs were designed based on structure-activity research, may help in the development of more peptide antibiotics.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arginine
/
Defensins
/
Cysteine
/
Anti-Infective Agents
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
ChemMedChem
Year:
2019
Document type:
Article