Design of multi-functional linear polymers that capture and neutralize a toxic peptide: a comparison with cross-linked nanoparticles.

In this paper, a library of multi-functional linear poly-N-isopropylacrylamide (pNIPAm) polymers having a range of molecular weights and functional groups were synthesized and their interaction with the hemolytic peptide, melittin, was examined. The linear pNIPAm (LPs) containing both tert-butyl group and carboxylic acids bound with the peptide by a combination of hydrophobic and electrostatic interactions and neutralized its toxicity. The melittin binding capacity and affinity of each LP was quantified and further compared with cross-linked multi-functional nanogel particles (NPs) having same combination of functional groups. The binding capacity of the LPs (weight of captured melittin/weight of LP) was independent of their molecular weight and was three times higher than that of previously reported NPs. The binding constant depended on the molecular weight of the LPs, showing the highest value of 1.1 × 108 (M-1) for a ∼1000 mer linear polymer with 40% tert-butyl group and 20% carboxylic acid. Comparison of the interactions of the LPs and NPs suggested the importance of the flexibility of the polymer chain in order to achieve high binding capacity and affinity.

[1]  Y. Miura,et al.  Preparation of nanogel-immobilized porous gel beads for affinity separation of proteins: Fusion of nano and micro gel materials , 2015 .

[2]  Y. Miura,et al.  Rational Design of Synthetic Nanoparticles with a Large Reversible Shift of Acid Dissociation Constants: Proton Imprinting in Stimuli Responsive Nanogel Particles , 2014, Advanced materials.

[3]  John M. Beierle,et al.  Epitope Discovery for a Synthetic Polymer Nanoparticle: A New Strategy for Developing a Peptide Tag , 2014, Journal of the American Chemical Society.

[4]  Y. Miura,et al.  Effect of physical properties of nanogel particles on the kinetic constants of multipoint protein recognition process. , 2014, Biomacromolecules.

[5]  Y. Miura,et al.  Interaction between synthetic particles and biomacromolecules: Fundamental study of nonspecific interaction and design of nanoparticles that recognize target molecules , 2014 .

[6]  Y. Okahata,et al.  Polymer nanoparticle-protein interface. Evaluation of the contribution of positively charged functional groups to protein affinity. , 2013, ACS applied materials & interfaces.

[7]  Arlo Z. Randall,et al.  Engineered synthetic polymer nanoparticles as IgG affinity ligands. , 2012, Journal of the American Chemical Society.

[8]  Y. Hoshino,et al.  ELISA-mimic screen for synthetic polymer nanoparticles with high affinity to target proteins. , 2012, Biomacromolecules.

[9]  Masahiko Nakamoto,et al.  Control of protein-binding kinetics on synthetic polymer nanoparticles by tuning flexibility and inducing conformation changes of polymer chains. , 2012, Journal of the American Chemical Society.

[10]  John M. Beierle,et al.  Temperature-responsive "catch and release" of proteins by using multifunctional polymer-based nanoparticles. , 2012, Angewandte Chemie.

[11]  Hiroyuki Koide,et al.  The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo , 2011, Proceedings of the National Academy of Sciences.

[12]  L. Lyon,et al.  Tunable Encapsulation of Proteins within Charged Microgels. , 2011, Macromolecules.

[13]  R. Haag,et al.  The role of dimension in multivalent binding events: structure-activity relationship of dendritic polyglycerol sulfate binding to L-selectin in correlation with size and surface charge density. , 2011, Macromolecular bioscience.

[14]  R. Haag,et al.  Synthesis of dendritic polyglycerol anions and their efficiency toward L-selectin inhibition. , 2011, Biomacromolecules.

[15]  Yu Hoshino,et al.  The evolution of plastic antibodies , 2011 .

[16]  R. Haag,et al.  Dendritic polyglycerol sulfates as multivalent inhibitors of inflammation , 2010, Proceedings of the National Academy of Sciences.

[17]  Y. Okahata,et al.  Affinity purification of multifunctional polymer nanoparticles. , 2010, Journal of the American Chemical Society.

[18]  Hiroyuki Koide,et al.  Recognition, neutralization, and clearance of target peptides in the bloodstream of living mice by molecularly imprinted polymer nanoparticles: a plastic antibody. , 2010, Journal of the American Chemical Society.

[19]  Hiroyuki Koide,et al.  Design of synthetic polymer nanoparticles that capture and neutralize a toxic peptide. , 2009, Small.

[20]  Sara Linse,et al.  Complete high‐density lipoproteins in nanoparticle corona , 2009, The FEBS journal.

[21]  Sara Linse,et al.  Inhibition of amyloid beta protein fibrillation by polymeric nanoparticles. , 2008, Journal of the American Chemical Society.

[22]  Y. Okahata,et al.  Peptide imprinted polymer nanoparticles: a plastic antibody. , 2008, Journal of the American Chemical Society.

[23]  善彦 島田,et al.  温度と pH に応答するジブロック共重合体の可逆的付加-開裂連鎖移動(RAFT)型ラジカル重合による合成 , 2007 .

[24]  Thomas Schrader,et al.  A noncovalent switch for lysozyme. , 2007, Journal of the American Chemical Society.

[25]  V. Rotello,et al.  Biomimetic interactions of proteins with functionalized nanoparticles: a thermodynamic study. , 2007, Journal of the American Chemical Society.

[26]  S. Radford,et al.  Nucleation of protein fibrillation by nanoparticles , 2007, Proceedings of the National Academy of Sciences.

[27]  Leonie Barner,et al.  Ambient Temperature RAFT Polymerization of Acrylic Acid Initiated with Ultraviolet Radiation in Aqueous Solution , 2007 .

[28]  T. Schrader,et al.  Artificial protein sensors. , 2007, Molecular bioSystems.

[29]  V. Rotello,et al.  Facial control of nanoparticle binding to cytochrome C. , 2007, Journal of the American Chemical Society.

[30]  T. Schrader,et al.  Dendrimeric bisphosphonates for multivalent protein surface binding. , 2006, Chemistry, an Asian journal.

[31]  C. Renner,et al.  Tuning linear copolymers into protein-specific hosts. , 2006, Angewandte Chemie.

[32]  Leonie Barner,et al.  RAFT Polymerization of N‐Isopropylacrylamide and Acrylic Acid under γ‐Irradiation in Aqueous Media , 2006 .

[33]  C. Renner,et al.  Arginine- and lysine-specific polymers for protein recognition and immobilization. , 2006, Journal of the American Chemical Society.

[34]  Jun Gao,et al.  Cross-Linker-Free N-Isopropylacrylamide Gel Nanospheres , 2003 .

[35]  Jun Gao,et al.  Influence of Reaction Conditions on the Synthesis of Self-Cross-Linked N-Isopropylacrylamide Microgels , 2003 .

[36]  Thomas P. Davis,et al.  Star polymer synthesis using trithiocarbonate functional β‐cyclodextrin cores (reversible addition–fragmentation chain‐transfer polymerization) , 2002 .

[37]  T. Schrader,et al.  The first synthetic receptor for the RGD sequence. , 2002, Organic letters.

[38]  T. Schrader,et al.  Optimization of a synthetic arginine receptor. Systematic tuning of noncovalent interactions. , 2001, The Journal of organic chemistry.

[39]  Failla,et al.  A chiral sensor for arginine and lysine , 2000, Organic letters.

[40]  T. Schrader.  Strong Binding of Alkylguanidinium Ions by Molecular Tweezers: An Artificial Selective Arginine Receptor Molecule with a Biomimetic Recognition Pattern , 1997 .