title: C-terminal functionalization of nylon-3 polymers: effects of C-terminal groups on antibacterial and hemolytic activities.
abstract: Nylon-3 polymers contain β-amino-acid-derived subunits and can be viewed as higher homologues of poly(α-amino acids). This structural relationship raises the possibility that nylon-3 polymers offer a platform for development of new materials with a variety of biological activities, a prospect that has recently begun to receive experimental support. Nylon-3 homo- and copolymers can be prepared via anionic ring-opening polymerization of β-lactams, and use of an N-acyl-β-lactam as coinitiator in the polymerization reaction allows placement of a specific functional group, borne by the N-acyl-β-lactam, at the N-terminus of each polymer chain. Controlling the unit at the C-termini of nylon-3 polymer chains, however, has been problematic. Here we describe a strategy for specifying C-terminal functionality that is based on the polymerization mechanism. After the anionic ring-opening polymerization is complete, we introduce a new β-lactam, approximately 1 equiv relative to the expected number of polymer chains. Because the polymer chains bear a reactive imide group at their C-termini, this new β-lactam should become attached at this position. If the terminating β-lactam bears a distinctive functional group, that functionality should be affixed to most or all C-termini in the reaction mixture. We use the new technique to compare the impact of N- and C-terminal placement of a critical hydrophobic fragment on the biological activity profile of nylon-3 copolymers. The synthetic advance described here should prove to be generally useful for tailoring the properties of nylon-3 materials.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, Wisconsin 53706, United States.
authors.forename: Jihua
authors.initials: J
authors.lastname: Zhang
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Markiewicz
authors.forename: Brendan P
authors.initials: BP
authors.lastname: Mowery
authors.forename: Bernard
authors.initials: B
authors.lastname: Weisblum
authors.forename: Shannon S
authors.initials: SS
authors.lastname: Stahl
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006461:Hemolysis; D006801:Humans; D007094:Imides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D009757:Nylons / Q000138:chemical synthesis* / Q000494:pharmacology; D058105:Polymerization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D047090:beta-Lactams / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D007094:Imides; D009757:Nylons; D047090:beta-Lactams