Abstract

In this proposal, we propose to combine (a) the latest protein engineering techniques with (b) stimuli-responsive polymer compositions to produce (c) responsive polymer-engineered protein (RP-EP) conjugates that have unique behaviors and uses. More specifically, we propose to conjugate temperature-, pH- or light-sensitive oligomers by one of their terminal ends to a specific site near or within the active recognition site of selected proteins, and then to apply a temperature, pH or light stimulus to tern """""""" (i.e., allow binding) or """"""""off"""""""" (i.e., either reduce the binding affinity, prevent binding altogether, or eject a previously-bound receptor) the binding of the target ligand or cell to the proteins's recognition site. The protein could be an antibody, an enzyme, a hormone, an integrin, albumin, streptavidin, or any other recognition protein. The protein could be an antibody, an enzyme, a hormone, an integrin, albumin, streptavidin, or any other recognition protein. The ability to turn on or off biological recognition processes on a molecular level should lead to many interesting, diverse and unique applications. In this proposal we focus on the affinity recognition process, and its applications in affinity separations, diagnostics and biosensors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM053771-02
Application #
2332021
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1996-02-01
Project End
1999-01-31
Budget Start
1997-02-01
Budget End
1998-01-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Cheung, Charles Y; Stayton, Patrick S; Hoffman, Allan S (2005) Poly(propylacrylic acid)-mediated serum stabilization of cationic lipoplexes. J Biomater Sci Polym Ed 16:163-79
Stayton, Patrick S; Ding, Zhongli; Hoffman, Allan S (2004) Smart polymer-streptavidin conjugates. Methods Mol Biol 283:37-43
Murthy, Niren; Campbell, Jean; Fausto, Nelson et al. (2003) Design and synthesis of pH-responsive polymeric carriers that target uptake and enhance the intracellular delivery of oligonucleotides. J Control Release 89:365-74
Jones, Rachel A; Cheung, Charles Y; Black, Fiona E et al. (2003) Poly(2-alkylacrylic acid) polymers deliver molecules to the cytosol by pH-sensitive disruption of endosomal vesicles. Biochem J 372:65-75
Malmstadt, Noah; Yager, Paul; Hoffman, Allan S et al. (2003) A smart microfluidic affinity chromatography matrix composed of poly(N-isopropylacrylamide)-coated beads. Anal Chem 75:2943-9
Murthy, Niren; Campbell, Jean; Fausto, Nelson et al. (2003) Bioinspired pH-responsive polymers for the intracellular delivery of biomolecular drugs. Bioconjug Chem 14:412-9
Shimoboji, Tsuyoshi; Ding, Zhongli L; Stayton, Patrick S et al. (2002) Photoswitching of ligand association with a photoresponsive polymer-protein conjugate. Bioconjug Chem 13:915-9
Lackey, Chantal A; Press, Oliver W; Hoffman, Allan S et al. (2002) A biomimetic pH-responsive polymer directs endosomal release and intracellular delivery of an endocytosed antibody complex. Bioconjug Chem 13:996-1001
Kyriakides, Themis R; Cheung, Charles Y; Murthy, Niren et al. (2002) pH-sensitive polymers that enhance intracellular drug delivery in vivo. J Control Release 78:295-303
Cheung, C Y; Murthy, N; Stayton, P S et al. (2001) A pH-sensitive polymer that enhances cationic lipid-mediated gene transfer. Bioconjug Chem 12:906-10

Showing the most recent 10 out of 16 publications