NIH grant: Evolution of Facial Amphiphilicity toward Alternating Copolymers as Antimicrobial Biomaterials (1R01GM164512-01)

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NIH grant 1R01GM164512-01: Evolution of Facial Amphiphilicity toward Alternating Copolymers as Antimicrobial Biomaterials
Institute: {'code': 'GM', 'abbreviation': 'NIGMS', 'name': 'National Institute of General Medical Sciences', 'admin_org_id': '12500024', 'admin_funding_url': ''}. PI: Chuanbing  Tang. Award: $320914.
Start: 2026-08-01T00:00:00.
Abstract
 This study investigates the design of synthetic macromolecules for the formation of secondary
structures, with a particular focus on facial amphiphilicity and its implications for antimicrobial
research against multidrug-resistant bacteria. Secondary structures are crucial for
biomacromolecule stability and function, influencing cellular processes and gene expression.
Facial amphiphilicity, defined by the separation of polar and nonpolar domains, is especially
significant in membrane interactions, playing a key role in antimicrobial efficacy.
 In peptides, facial amphiphilicity enables effective interactions with bacterial membranes,
enhancing antimicrobial activity. While synthetic polymers aim to replicate this property,
challenges remain in maintaining sequence control and structural integrity. This project will
address these challenges by focusing on two key designs: (1) alternating copolymers with spatial
arrangements of charges and hydrophobic groups to promote the formation of helical structures
with global amphiphilicity, and (2) synthetic polypeptides that combine local and global
amphiphilicity, enabling more precise control over macromolecular interactions.
 The proposed synthetic macromolecules are designed to fold into distinct, phase-segregated
faces in aqueous environments. By minimizing entropic loss and lowering energy barriers for
conformational rearrangements, they represent a significant improvement over traditional random
copolymer. Additionally, the defined spatial segregation of hydrophobic and cationic groups
enhances their ability to selectively target bacterial cells while minimizing cytotoxicity toward
mammalian cells, making them safer for therapeutic applications.
 Facially amphiphilic polymers may also excel in biofilm penetration and disruption due to their
optimized interaction with the extracellular matrix. This project aims to expand the use of these
polymers into anti-biofilm applications, further enhancing their therapeutic potential.

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