Abstract

This is an application for renewed support of an onging program of study on the physicochemical and biological properties of proteins and peptides in solution with emphasis on their interaction with each other and with small molecules. The following research is proposed: (1) fluorometric determination of the binding constants of the phenothiazine tranquilizers, chlorpromazine and trifluoperazine, and the control drug promethazine to mouse brain tubulin, and extension of these studies to psychoactive drugs from different classes of chemical compounds; (2) elucidation of the mechanisms whereby enkephalin and substance P inhibit the reassembly of tubulin into microtubules; (3) a CD study of the interaction of bradykinin and other peptide hormones with GM1-ganglioside and cerebroside sulfate; (4) continuation and extension of our CD and NMR studies on the solution conformation of bradykinin to alpha-aminoisobutyric acid-containing analogues and a 19F NMR study of the binding of (p-fluorophenylalanine8)-bradykinin to bovine uterine membranes; (5) completion of our CD and 13C NMR investigation of the solution conformation of the model peptide, trilysine; and (6) continuation and extension of our theoretical calculation on the mass transport of interacting macromolecules to include the antigen-antibody reaction, the isomerization of creatine kinase and the quantification of ligand-binding by counter ion electrophoresis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028793-34
Application #
3276088
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1981-06-01
Project End
1986-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
34
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Cann, J R (1993) Theoretical studies on the mobility-shift behavior of binary protein-DNA complexes. Electrophoresis 14:669-79
Winzor, D J; Munro, P D; Cann, J R (1991) Experimental and theoretical studies of rate constant evaluation for the solute-matrix interaction in affinity chromatography. Anal Biochem 194:54-63
Yang, S N; Wolska-Klis, M M; Cann, J R (1991) Gel electrophoresis of reacting macromolecules. Rate-limited self-association. Anal Biochem 196:192-8
Cann, J R (1990) Analysis of the gel electrophoresis of looped protein-DNA complexes by computer simulation. J Mol Biol 216:1067-75
Appu Rao, A G; Cann, J R; Stewart, J M et al. (1990) Evidence of neuropeptide bivalency in the interaction of substance P with cerebroside sulfate. Int J Pept Protein Res 35:258-62
Cann, J R (1989) Phenomenological theory of gel electrophoresis of protein-nucleic acid complexes. J Biol Chem 264:17032-40
Rao, A G; Stewart, J M; Vavrek, R J et al. (1989) A fluorometric study of the interaction of bradykinin with lipids. Biochim Biophys Acta 997:278-83
Werner, W E; Cann, J R; Schachman, H K (1989) Boundary spreading in sedimentation velocity experiments on partially liganded aspartate transcarbamoylase. A ligand-mediated isomerization. J Mol Biol 206:231-7
Cann, J R; Rao, A G; Winzor, D J (1989) Numerical and experimental demonstrations of the need for caution in the use of zonal gel chromatography for characterizing ligand interactions with small acceptors. Arch Biochem Biophys 270:173-83
Cann, J R; York, E J; Stewart, J M et al. (1988) Small zone gel chromatography of interacting systems: theoretical and experimental evaluation of elution profiles for kinetically controlled macromolecule-ligand reactions. Anal Biochem 175:462-73

Showing the most recent 10 out of 21 publications