Boyer C., Bulmus, V., Davis T. P., Ladmiral V., Liu J., Perrier S. Chemical Review 2009, 109, ( 作者按姓氏字母顺序排列。本人负责 Bioconjugates 部分的编写 ) RAFT 聚合在生物领域中的应用（一）

Introduction 1. Biomolecule-Polymer Conjugates ( 生物分子和高分子复合物 ) 胚胎干细胞对特定老鼠基因的改造和干扰

Biomolecule-polymer conjugate Attachment of polymer to biomolecules Improves their stability, solubility and biocompatibility. It also benefits for the biomolecule’s self-assembly, patterning and phase behavior. Maynard, H. D., Heredia K. L. Organic & Biomolecular Chemistry, 2007, 5 (1):  Medicine and biotechnology 1 1. Vincent, M. J., Duncan, R, Trends in Biotechnology, 2005, 24,  Bio-separations 2 2. Roy, I., Gupta, M., N., Chemistry and Biology, 2003, 10,  Biosensors 3 3. Ghica, M. E., Brett, C. M. A., Electroanalysis, 2006, 18,  Diagnosis of diseases 4 4. Duncan, R., Nature Reviews of Drug Discovery, 2003, 2,  Drug delivery 5 5. Kikuchi, A., Okano, T., Advanced Drug Delivery Review, 2002, 54, 53–77. Introduction Why biomolecule-Polymer Conjugates?

 “Graft to”  “Graft from” In-situ grafting Initiator

Introduction Methods to Prepare Biomolecule-Polymer Conjugates Biomolecule Drawbacks:  Multiple steps  Complicated purification process  Unavoidable non-specific adsorption  Multi-site attachment  Low yield a) Post-polymerization Conjugation Biomolecule-polymer conjugate Polymer

Introduction Methods to Prepare Biomolecule -polymer Conjugates In situ polymerization Advantages  Less steps  Easy to control b) In situ polymerization  Less-purification  High yield Biomolecule Biomolecule -polymer conjugate

Introduction Reversible Addition Fragmentation Chain-Transfer (RAFT) Polymerisation b.RAFT polymerization  Polymerize more versatile monomers in more flexible reaction conditions for a wide range of polymeric architectures  Get rid of the metal catalyst which might complex with some functional groups on proteins and damage the protein bioactivity. a. Atom transfer radical polymerization (ATRP)  Synthesize well-defined polymeric architectures with predictable MW and PDI  Supply a good technique to prepare well-defined protein-polymer conjugate

2. In-situ Synthesis of Protein-polymer Conjugates J. Liu, V. Bulmus, D. L. Herlambang, C. Barner-Kowollik, M. H. Stenzel, T. P. Davis, Angew. Chem. Int. Ed. 2007, 46,

3. Heterotelechelic Protein-Polymer-Biomolecule Conjugates Jingquan Liu, Huiyun Liu, Volga Bulmus, Lei Tao, Cyrille Boyer, Thomas P. Davis, Journal of Polymer Science Part A: Polymer Chemistry, 2010, 48, （ IF ， ）.

2.1 Modification of Bifunctional RAFT Agent

2.2 Conjugation of Bifunctional RAFT Agent to Protein

2.3 Characterization---- GPC analysis

2.3 Characterization----Cleavage test

2.4 Characterization----End group check

3. Summary  Bifunctional TRITT was successfully modified with pyridyl disulfide groups on both sides  The conjugation of bifunctional RAFT revealed that only one BSA was attached on RAFT  In-situ polymerization lead to synthesis of bioconjugates with thiol reactive functional group in one step  Sometimes research turned out to be much easier?

4. Conjugate of H 2 NO-KYNPKDKLLY with polymers as anthrax toxin inhibitor This work was done with Prof Heather Maynard at University of California Los Angeles (UCLA) Jingquan Liu, Volga Bulmus, Thomas P. Davis, Ronald Li and Heather D Maynard ， Macromolecules, 48, 8-14, (IF, 5.167)

Tailoring the end groups and cleavage tests

Eki Setijadi, Lei Tao, Jingquan Liu *, Cyrille Boyer, Zhongfan Jia and Thomas P. Davis, Biomacromolecules, 2009, 10 (9), pp 2699–2707. Cholesterol Attachment and cyclodextrIn Complex

Manipulation of the Bioactivity of Glucose Oxidase via RAFT Controlled Surface Modification X. Luo, J. Liu*, G. Liu, R. Wang, Z. Liu ， J. Polym. Sci. Part A Polym. Chem, 2012 ， 50, 14,

Micelles/Vesicles as drug carrier