Highly Efficient ‘‘Grafting From’’ an a-Helical Polypeptide Backbone by Atom Transfer Radical Polymerization a Jianxun Ding, Chunsheng Xiao, Zhaohui Tang, Xiuli Zhuang, Xuesi Chen* Introduction Synthetic polypeptides are one of the most important biocompatible and biodegradable polymers, which have well-defined secondary structures and have been studied for biomedical applications, such as tissue engineering, [1–4] drug and gene delivery, [5–9] bioadhesion, [10–13] antimicrobial properties, [14–16] and as biosensors and diagnostics. [17–20] However, their applications are limited because of their insolubility or pH-dependent solubility in water and lack of functional groups able to be functionalized efficiently. [21,22] These disadvantages can be overcome by modifying the polypeptides with functional groups. Functional polypep- tides have attracted considerable attention for their potential use in the preparation of modified block, graft, branched, or ring copolymers, and by conjugating with biologically active agents. [21,23–26] The synthesis of polypeptides has been reported using a well-studied ring-opening polymerization (ROP) of N-carboxyanhydride (NCA). Functional polypeptides can be prepared through two approaches: 1) ROP of monomers with various functional groups, [21,27–31] or 2) postpolymer- ization modification of side groups on the polypeptides (‘‘grafting onto’’ methods), such as condensation, [32,33] aminolysis, [34,35] ester exchange, [36,37] click chemistry, [23–26] and so on. The synthesis of functional polypeptides by the first approach has been limited by the difficulties Communication J. X. Ding, C. S. Xiao, Z. H. Tang, X. L. Zhuang, X. S. Chen Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China Fax: þ86 431 85262112; E-mail: xschen@ciac.jl.cn J. X. Ding, C. S. Xiao Graduate University of the Chinese Academy of Sciences, Beijing 100039, P. R. China a : Supporting information for this article is available at the bottom of the article’s abstract page, which can be accessed from the journal’s homepage at http://www.mbs-journal.de, or from the author. Because of their favorable biodegradability, biocompatibility, regular secondary structures, and stimuli-responsiveness, synthetic polypeptides have attracted more and more attention in the biomedical material field. In this work, a novel thermo-responsive graft polypeptide, poly(L-glutamate)-graft-poly(2-(2-methoxyethoxy)ethyl methacrylate) (PLG-g-PMEO 2 MA), is prepared through a combination of ring-opening polymerization and atom transfer radical polymerization. The structure of PLG-g-PMEO 2 MA is confirmed by FT-IR, 1 H NMR, and GPC analyses. The phase transition temperature of PLG-g- PMEO 2 MA is adjustable by varying the NaCl concentration in aqueous solution. PLG-g-PMEO 2 MA adopts a-helical con- formations both in aqueous solution at 25 and 60 8C and even in the solid state. In addition, PLG-g-PMEO 2 MA forms stimuli-responsive micelles with an a-helical core and a thermo-responsive shell in water. 192 Macromol. Biosci. 2011, 11, 192–198 ß 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com DOI: 10.1002/mabi.201000238