Boc-L-leucine methyl ester

This review summarizes recent advances in the design and synthesis of amino-acid-based block copolymers by reversible addition-fragmentation chain transfer (RAFT) polymerization of amino-acid-bearing monomers. We will mainly focus on stimuli-responsive block copolymers, such as pH-, thermo-, and dual-stimuli-responsive block copolymers, and self-assembled block copolymers, including amphiphilic and double-hydrophilic block copolymers having tunable chiroptical properties. We will also highlight recent results in RAFT synthesis of amino-acid-based copolymers having various properties, such as catalytic and optoelectronic properties, cross-linked block copolymer micelles, unimolecular micelles, and organic-inorganic hybrids.

Developing safe and effective nanocarriers for multitype of delivery system is advantageous for several kinds of successful biomedicinal therapy with the same carrier. In the present study, we have designed amino acid biomolecules derived hybrid block copolymers which can act as a promising vehicle for both drug delivery and gene transfer. Two representative natural chiral amino acid-containing (l-phenylalanine and l-alanine) vinyl monomers were polymerized via reversible addition-fragmentation chain transfer (RAFT) process in the presence of monomethoxy poly(ethylene glycol) based macro-chain transfer agents (mPEGn-CTA) for the synthesis of well-defined side-chain amino-acid-based amphiphilic block copolymers, monomethoxy poly(ethylene glycol)-b-poly(Boc-amino acid methacryloyloxyethyl ester) (mPEGn-b-P(Boc-AA-EMA)). The self-assembled micellar aggregation of these amphiphilic block copolymers were studied by fluorescence spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). Potential applications of these hybrid polymers as drug carrier have been demonstrated in vitro by encapsulation of nile red dye or doxorubicin drug into the core of the micellar nanoaggregates. Deprotection of side-chain Boc- groups in the amphiphilic block copolymers subsequently transformed them into double hydrophilic pH-responsive cationic block copolymers having primary amino groups in the side-chain terminal. The DNA binding ability of these cationic block copolymers were further investigated by using agarose gel retardation assay and AFM. The in vitro cytotoxicity assay demonstrated their biocompatible nature and these polymers can serve as "smart" materials for promising bioapplications.

A general and facile strategy was developed to prepare biocompatible peptide side-chain polymeric materials via reversible addition-fragmentation chain transfer (RAFT) polymerization. Three new dipeptide based monomers, Boc-Phe-Phe-oxyethyl methacrylate (Boc-FF-EMA), Boc-Ile-Phe-oxyethyl methacrylate (Boc-IF-EMA) and Boc-Val-Phe-oxyethyl methacrylate (Boc-VF-EMA), were synthesized and subsequently polymerized by RAFT process to afford well-defined peptide side-chain polymers, P(Boc-dipep-EMA), with controlled molecular weight, narrow polydispersity and precise chain end functionality. Further, a monomethoxy poly(ethylene glycol) (mPEG) based macro-chain transfer agent was employed for RAFT polymerization of these monomers to prepare well defined amphiphilic block copolymers, mPEG-b-P(Boc-dipep-EMA). Subsequent deprotection of side-chain Boc groups produced pH responsive homo- and block copolymers with primary amine moieties at the side chains. The cationic surface charge of various polymeric architectures was studied using dynamic light scattering (DLS) measurements. Atomic force microscopy (AFM) was employed to investigate the self-assembly of block copolymers. The in vitro biocompatibility to HeLa cells was investigated with these polymers to confirm their minimum cytotoxicity. These polymers have great potential for the pH-sensitive delivery of small interfering RNA (siRNA) owing to their interesting phase transition behaviour and biocompatibility.