Designed amino acid ATRP initiators for the synthesis of biohybrid materials.
A synthetic strategy to prepare peptide-polymer conjugates with precise sites of attachment is described. Amino acids modified with atom transfer radical polymerization (ATRP) initiators for the polymerization of styrenes and methacrylates were prepared. Fmoc-4-(1-chloroethyl)-phenylalanine (5) was synthesized in four steps from Fmoc-tyrosine. HATU-mediated amidation with glycine-OMe resulted in dipeptide (6). The initiator was effective for Cu(I)/bipyridine mediated bulk polymerization of styrene. Kinetic studies indicated a controlled polymerization, with high conversion (97%), and a polydispersity index (PDI) of 1.25. Fmoc-O-(2-bromoisobutyryl)-serine tert-butyl ester (10) was synthesized from Fmoc-Ser(OTrt)-OH in three steps. This initiator was employed in the ATRP of 2-hydroxyethyl methacrylate (HEMA), and kinetic studies indicated a controlled polymerization. Different monomer to initiator ratios resulted in poly(HEMA) of different molecular weights and narrow PDIs (1.14-1.25). Conversions were between 70 and 99%. HEMA modified with N-acetyl-D-glucosamine (GlcNAc) was also polymerized to 84% conversion and the resulting PDI was 1.19. The t-butyl ester protecting group of 10 was removed, and the resulting amino acid (11) was incorporated into VM(11)VVQTK by standard solid-phase peptide synthesis. Polymerization resulted in the glycopolymer-peptide conjugate in 93% conversion and a PDI of 1.14.
Broyer
Rebecca M
RM
Department of Chemistry and Biochemistry and the California NanoSystems Institute, University of California, 607 Charles E. Young Drive East, Los Angeles, California 90096-1569, USA.
Quaker
Grace M
GM
Maynard
Heather D
HD
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry; D005449:Fluorenes / Q000138:chemical synthesis / Q000737:chemistry; D008689:Methacrylates / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis*; D011109:Polymethacrylic Acids / Q000737:chemistry; D011137:Polystyrenes / Q000138:chemical synthesis; D012694:Serine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D013343:Styrenes / Q000737:chemistry
D000596:Amino Acids; D004151:Dipeptides; D005449:Fluorenes; D008689:Methacrylates; D010455:Peptides; D011108:Polymers; D011109:Polymethacrylic Acids; D011137:Polystyrenes; D013343:Styrenes; C526609:fluorenylmethoxycarbonyl-4-(1-chloroethyl)phenylalanine; C526610:fluorenylmethoxycarbonyl-O-(2-bromoisobutyryl)serine; D012694:Serine; D010649:Phenylalanine; C005044:hydroxyethyl methacrylate