New Platform Uncovers Novel Peptides for Polysaccharide Binding

Polysaccharides are ubiquitous biopolymers critical for various biological functions, including forming bacterial biofilms, acting as structural components in cell walls, and serving as key elements in drug delivery systems. The ability to specifically target and interact with these complex molecules using peptides holds immense therapeutic and industrial potential. However, existing methods for discovering such peptides often suffer from biases or limited diversity in their libraries. This study developed a novel, unbiased platform combining yeast display and bacterial genomic libraries to discover new polysaccharide-binding peptides with enhanced specificity and affinity.

The study successfully identified 14 novel peptide sequences that exhibited high affinity and specificity for various target polysaccharides. Binding affinities (Kd) for these peptides ranged significantly, from 50 nM to 750 nM, indicating a broad spectrum of binding strengths. One standout peptide, designated PBP-ALG1, demonstrated exceptional affinity for alginate with a Kd of 75 nM, representing a 3.2-fold improvement over previously reported synthetic binders. PBP-ALG1 significantly inhibited Pseudomonas aeruginosa biofilm formation in vitro, achieving a 55% reduction in biofilm biomass at a concentration of 5 µM (p<0.0001) compared to untreated controls. Another novel peptide, PBP-CEL2, exhibited high specificity for bacterial cellulose with a Kd of 110 nM, showing negligible cross-reactivity (<5% binding) with other tested polysaccharides. Overall, 85% of the characterized peptides displayed high specificity for their respective target polysaccharides, with minimal off-target binding.