Surface Design for Immobilization of an Antimicrobial Peptide Mimic for Efficient Anti-Biofouling.

Abshar Hasan,Kunal Tewari,Kyueui Lee,Phillip B Messersmith,King Hang Aaron Lau,Karen Faulds,Michelle Maclean,Lalit M Pandey

doi:10.1002/chem.202000746

Abstract

Microbial surface attachment negatively impacts a wide range of devices from water purification membranes to biomedical implants. Mimics of antimicrobial peptides (AMPs) constituted from poly(N‐substituted glycine) „peptoids“ are of great interest as they resist proteolysis and can inhibit a wide spectrum of microbes. We investigate how terminal modification of a peptoid AMP‐mimic and its surface immobilization affect antimicrobial activity. We also demonstrate a convenient surface modification strategy for enabling alkyne–azide „click“ coupling on amino‐functionalized surfaces. Our results verified that the N‐ and C‐terminal peptoid structures are not required for antimicrobial activity. Moreover, our peptoid immobilization density and choice of PEG tether resulted in a „volumetric“ spatial separation between AMPs that, compared to past studies, enabled the highest AMP surface activity relative to bacterial attachment. Our analysis suggests the importance of spatial flexibility for membrane activity and that AMP separation may be a controlling parameter for optimizing surface anti‐biofouling.

Highlights

Bacterial adhesion and colonization on implantable biomedical devices and the consequent infection contribute to 40–70 % of hospital-acquired infections (HAI).[1]
Many existing antimicrobial agents suffer from a narrow spectrum of activity and a rising resistance against their activities.[6b,7] Antimicrobial peptides (AMPs) are being investigated to overcome these issues,[6] but they are degraded by proteases secreted by both human hosts and bacteria.[8]
A number of groups have demonstrated peptoid AMP mimics that exhibit high activity.[6b,8a,11] One such peptoid has been synthesized as part of a surface grafted peptoid brush but a high level of overall bacterial attachment was observed.[12]

Summary

Introduction

Bacterial adhesion and colonization on implantable biomedical devices and the consequent infection contribute to 40–70 % of hospital-acquired infections (HAI).[1]. A number of groups have demonstrated peptoid AMP mimics that exhibit high activity.[6b,8a,11] One such peptoid has been synthesized as part of a surface grafted peptoid brush but a high level of overall bacterial attachment was observed.[12] Natural AMPs such as hLf1-11, LL-37, and melamine have been immobilized with varying results.[6,8c,13] These studies apply bioconjugation techniques such as maleimide-

Results

Conclusion