title: Polymerizable vancomycin derivatives for bactericidal biomaterial surface modification: structure-function evaluation.
abstract: Surface modification of implantable biomaterials with biologically active functionalities, including antimicrobials, has wide potential for addressing implant-related design problems. Here, four polymerizable vancomycin derivatives bearing either acrylamide or poly(ethylene glycol) (PEG)-acrylate were synthesized and then polymerized through a surface-mediated reaction. Functionalization of vancomycin at either the V(3) or the X(1) position decreased monomeric activity by 6-75-fold depending on the modification site and the nature of the adduct (P < 0.08 for all comparisons). A 5000 Da PEG chain showed an order of magnitude decrease in activity relative to a 3400 Da counterpart. Molecular dynamics computational simulations were used to explore the mechanisms of this decreased activity. Assays were also conducted to demonstrate the utility of a living radical photopolymerization to create functional, polymeric surfaces with these monomers and to demonstrate surface-based activity against Staphylococcus epidermidis . In particular, the vancomycin-PEG-acrylate derivatives demonstrated a 7-8 log reduction in bacterial colony forming units (CFU) with respect to nonfunctionalized control surfaces.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA.
authors.forename: McKinley C
authors.initials: MC
authors.lastname: Lawson
authors.forename: Richard
authors.initials: R
authors.lastname: Shoemaker
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Hoth
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Bowman
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001422:Bacterial Adhesion; D020099:Coated Materials, Biocompatible / Q000627:therapeutic use*; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D015394:Molecular Structure; D010777:Photochemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers; D019736:Prostheses and Implants / Q000382:microbiology; D016459:Prosthesis-Related Infections / Q000517:prevention & control; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D020099:Coated Materials, Biocompatible; D011108:Polymers; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols; D014640:Vancomycin