
헤파린 결합 단백질(HBP)에는 그람 음성 세균에 대한 강력한 항균 활성을 가진 숨겨진 항균 펩타이드가 존재한다. 이러한 펩타이드는 헤파린과 LPS에 대한 높은 결합 친화도를 보이며, 세균 세포벽을 파괴하여 항균 작용을 나타낸다.


coremsg

Glycosaminoglycan (GAG)-binding proteins regulating essential processes such as cell growth and migration are essential for cell homeostasis. As both GAGs and the lipid A disaccharide core 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 correlation between heparin and LPS binding. Structural characterization of these AMPs shows that heparin or LPS recognition promotes a conformational arrangement that favors binding. Among all analogs, HBP-5 displayed the highest affinity for both heparin and LPS, with antimicrobial activities against gram-negative bacteria at the nanomolar range. These results suggest that GAG-binding proteins are involved in LPS recognition, which allows them to act also as antimicrobial proteins. Some of the peptides reported here, particularly HBP-5, constitute a new class of AMPs with specific activity against gram-negative bacteria.

### Competing Interest Statement

The authors have declared no competing interest.

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

그람-음성-세균에-선택적으로-작용하는-새로운-항균-펩타이드-발굴을-위한-헤파린옴-탐색


그람 음성 세균에 선택적으로 작용하는 새로운 항균 펩타이드 발굴을 위한 헤파린옴 탐색
