Mining the heparinome for cryptic antimicrobial peptides that selectively kill Gram-negative bacteria

ABSTRACT: Glycosaminoglycan (GAG)-binding proteins regulate essential processes such as cell growth and migration. As both GAGs and the lipid A disaccharide of Gram-negative bacteria contain negatively charged disaccharide units, we hypothesized that GAG-binding proteins could also recognize LPS and enclose cryptic antibiotic motifs. Here, we report novel antimicrobial peptides (AMPs) derived from heparin-binding proteins (HBPs), with specific activity against Gram-negative bacteria and high LPS binding. We used computational tools to locate antimicrobial regions in 82% of HBPs, most of those colocalizing with putative heparin binding sites. To validate these results, we synthesized five candidates [HBP1-5] that showed remarkable activity against Gram-negative bacteria, as well as a strong correlati

SUBMITTER: Roberto Bello-Madruga 

PROVIDER: S-SCDT-10_1038-S44320-025-00120-6 | biostudies-other |

REPOSITORIES: biostudies-other