Prev. Article Next Article Table of Contents

Article

Designed Amino Acid ATRP Initiators for the Synthesis of Biohybrid Materials

Supporting Info

Rebecca M. Broyer, Grace M. Quaker, and Heather D. Maynard*

Department of Chemistry and Biochemistry and the California NanoSystems Institute, University of California, 607 Charles E. Young Drive East, Los Angeles, California 90096-1569

J. Am. Chem. Soc., 2008, 130 (3), pp 1041–1047

DOI: 10.1021/ja0772546

Publication Date (Web): December 28, 2007

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, maynard@chem.ucla.edu

Abstract

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.