O‐Mannosylation Affords a Glycopeptide Hydrogel with Inherent Antibacterial Activities against E. coli via Multivalent Interactions between Lectins and Supramolecular Assemblies

Abstract

Multivalent carbohydrate–lectin interactions play a crucial role in bacterial infection. Biomimicry of multivalent glycosystems represents a major strategy in the repression of bacterial growth. In this study, a new kind of glycopeptide (Naphthyl‐Phe‐Phe‐Ser‐Tyr, NMY) scaffold with mannose modification is designed and synthesized, which is able to perform supramolecular self‐assembly with the assistance of catalytic enzyme, and present multiple mannose ligands on its self‐assembled structure to target mannose‐binding proteins. Relying on multivalent carbohydrate–lectin interactions, the glycopeptide hydrogel is able to bind Escherichia coli (E. coli) in high specificity, and result in bacterial adhesion, membrane disruption and subsequent cell death. In vivo wound healing assays reveal that this glycopeptide hydrogel exhibits considerable potentials for promoting wound healing and preventing E. coli infection in a full‐thickness skin defect mouse model. Therefore, through a specific mannose–lectin interaction, a biocompatible hydrogel with inherent antibacterial activity against E. coli is achieved without the need to resort to antibiotic or antimicrobial agent treatment, highlighting the potential role of sugar‐coated nanomaterials in wound healing and control of bacterial pathogenesis.

Recently Developed Carbohydrate Based Gelators and Their Applications

“…Upon incubating the bacteria with the hydrogel, visible bactericidal activity was observed and it increased as the concentration of the hydrogel increased, as depicted in Figure 70, section B [125]. To investigate the specificity of the hydrogel to mannose-binding proteins, Staphylococcus aureus was also tested as it does not contain these types of proteins that would form interactions with mannose [125]. The results illustrated that the gel had no effect on S. aureus which further confirms their hypothesis.…”

“…Two other captivating examples were reported in the literature utilizing the same design principles of a molecule with a naphthyl group attached to a tetrapeptide unit containing a phosphate group, incorporating ALP as the enzymatic stimuli for self-assembly and a sugar moiety for lectin binding. A glycopeptide-based gelator composed of Dmannose and Phe-Phe-Ser-Tyr(H 2 PO 3 ) was reported as an antibacterial agent as well as for wound healing applications [125]. As shown in Figure 70, section A, the mannose was specifically included to enable mannose-lectin interactions that would bring about protein agglutination of the lectin Concanavalin A (ConA), disturbance of the cell membrane and bacterial adhesion [125].…”

“…A glycopeptide-based gelator composed of Dmannose and Phe-Phe-Ser-Tyr(H 2 PO 3 ) was reported as an antibacterial agent as well as for wound healing applications [125]. As shown in Figure 70, section A, the mannose was specifically included to enable mannose-lectin interactions that would bring about protein agglutination of the lectin Concanavalin A (ConA), disturbance of the cell membrane and bacterial adhesion [125]. The hydrogel formed at 1 wt % after the phosphate group was cleaved in the presence of ALP and it had the typical fibrous morphology.…”

“…The hydrogel formed at 1 wt % after the phosphate group was cleaved in the presence of ALP and it had the typical fibrous morphology. The antibacterial properties were tested using cultures of Escherichia coli; they employed strain ATCC-25922 which has a mannose-binding protein FimH adhesion incorporated in its cellular model [125]. Upon incubating the bacteria with the hydrogel, visible bactericidal activity was observed and it increased as the concentration of the hydrogel increased, as depicted in Figure 70, section B [125].…”

“…The antibacterial properties were tested using cultures of Escherichia coli; they employed strain ATCC-25922 which has a mannose-binding protein FimH adhesion incorporated in its cellular model [125]. Upon incubating the bacteria with the hydrogel, visible bactericidal activity was observed and it increased as the concentration of the hydrogel increased, as depicted in Figure 70, section B [125]. To investigate the specificity of the hydrogel to mannose-binding proteins, Staphylococcus aureus was also tested as it does not contain these types of proteins that would form interactions with mannose [125].…”