title: Endolytic, pH-responsive HPMA-b-(L-Glu) copolymers synthesized via sequential aqueous RAFT and ring-opening polymerizations.
abstract: A facile synthetic pathway for preparing block copolymers with pH-responsive L-glutamic acid segments for membrane disruption is reported. Aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization was first used to prepare biocompatible, nonimmunogenic poly[N-(2-hydroxypropyl)methacrylamide]. This macro chain transfer agent (CTA) was then converted into a macroinitiator via simultaneous aminolysis and thiol-ene Michael addition using the primary amine substituted N-(3-aminopropyl)methacrylamide. This macroinitiator was subsequently utilized in the ring-opening polymerization of the N-carboxyanhydride monomer of γ-benzyl-L-glutamate. After deprotection, the pH-dependent coil-to-helix transformations of the resulting HPMA-b-(L-Glu) copolymers were monitored via circular dichroism spectroscopy. HPMA segments confer water solubility and biocompatibility while the L-glutamic acid repeats provide reversible coil-to-helix transitions at endosomal pH values (~5-6). The endolytic properties of these novel [HPMA-b-(L-Glu)] copolymers and their potential as modular components in drug carrier constructs was demonstrated utilizing red blood cell hemolysis and fluorescein release from POPC vesicles.
authors.affiliation: The Department of Polymer Science and Engineering and §The Department of Chemistry and Biochemistry, The University of Southern Mississippi , Hattiesburg, Mississippi 39406, United States.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Holley
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Ray
authors.forename: Wenming
authors.initials: W
authors.lastname: Wan
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Savin
authors.forename: Charles L
authors.initials: CL
authors.lastname: McCormick
mesh_terms: D000178:Acrylamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D002942:Circular Dichroism; D004912:Erythrocytes / Q000378:metabolism; D006461:Hemolysis; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D015394:Molecular Structure; D058105:Polymerization; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000178:Acrylamides; D001672:Biocompatible Materials; D014867:Water; C032976:N-(2-hydroxypropyl)methacrylamide