PMID- 22946923 OWN - NLM STAT- MEDLINE DCOM- 20130122 LR - 20120919 IS - 1520-5126 (Electronic) IS - 0002-7863 (Linking) VI - 134 IP - 37 DP - 2012 Sep 19 TI - Control of protein-binding kinetics on synthetic polymer nanoparticles by tuning flexibility and inducing conformation changes of polymer chains. PG - 15209-12 AB - Although a number of procedures to create synthetic polymer nanoparticles (NPs) with an intrinsic affinity to target biomacromolecules have been published, little has been reported on strategies to control the binding kinetics of target recognition. Here, we report an enzyme-mimic strategy to control binding/dissociation rate constants of NPs, which bind proteins through multipoint interactions, by taking advantage of the temperature-responsive coil-globule phase transition of poly-N-isopropylacrylamide (PNIPAm)-based NPs. PNIPAm NPs with a "flexible" random-coil conformation had a faster binding rate than NPs with a "rigid" globule conformation; however, the dissociation rate constant remained unchanged, resulting in stronger affinity. The dissociation rate of the "flexible" NPs was decelerated by the "induced-fit"-type conformation change of polymers around the coil-globule phase transition temperature, resulting in the formation of the most stable NP-protein complexes. These results provide a guide for designing plastic antibodies with tailor-made binding kinetics and equilibrium constants. FAU - Hoshino, Yu AU - Hoshino Y AD - Department of Chemical Engineering, Kyushu University, 744 Motooka, Fukuoka 819-0395, Japan. yhoshino@chem-eng.kyushu-u.ac.jp FAU - Nakamoto, Masahiko AU - Nakamoto M FAU - Miura, Yoshiko AU - Miura Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120906 PL - United States TA - J Am Chem Soc JT - Journal of the American Chemical Society JID - 7503056 RN - 0 (Polymers) SB - IM MH - Kinetics MH - Molecular Conformation MH - *Nanoparticles MH - Polymers/*chemistry EDAT- 2012/09/06 06:00 MHDA- 2013/01/23 06:00 CRDT- 2012/09/06 06:00 PHST- 2012/09/06 06:00 [entrez] PHST- 2012/09/06 06:00 [pubmed] PHST- 2013/01/23 06:00 [medline] AID - 10.1021/ja306053s [doi] PST - ppublish SO - J Am Chem Soc. 2012 Sep 19;134(37):15209-12. doi: 10.1021/ja306053s. Epub 2012 Sep 6.