BIOCHEMICAL CHARACTERIZATION OF P-GLYCOPROTEIN

Project: Research project

Description

A major problem in cancer chemotherapy remains the development of tumor
cell resistance to multiple chemotherapeutic agents. Overexpression of
the multidrug resistance gene (MDR1) leads to the appearance of P-
glycoprotein (P-gp) in the plasma membrane of tumor cells. This protein
functions as a drug efflux pump resulting in tumor cell resistance to many
cytotoxic drugs. The long-term objectives of this grant proposal are (1)
to further understand the structural determinants and biochemical
characteristics of P-gp, and (2) to unravel the molecular mechanism by
which P-gp can recognize a wide variety of lipophilic agents including
both cytotoxic drugs and MDR modulators. The specific aims of this
proposal are to (1) synthesize specific photoaffinity probes, (2)
investigate the modes of drug interaction with P-gp, (3) identify drug
binding domains of P-gp, and (4) purify drug binding fragments of P-gp and
identify the specific amino acid sequences of the drug binding site(s).
These studies will increase our knowledge of the biochemistry and
molecular nature of P-gp and could provide a framework for the rational
design and synthesis of effective MDR modulators.
StatusFinished
Effective start/end date5/1/925/31/01

Funding

  • National Institutes of Health
  • National Institutes of Health: $158,996.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $140,352.00
  • National Institutes of Health

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P-Glycoprotein
Pharmaceutical Preparations
Multiple Drug Resistance
Paclitaxel
Binding Sites
Vinblastine
Protein Kinase C-alpha
Tamoxifen
MDR Genes
Cyclosporine
Neoplasms
Amino Acid Sequence
Phosphorylation
Organized Financing
Site-Directed Mutagenesis
Cytotoxins
Peptides
Drug Interactions
Biochemistry
Genes

ASJC

  • Medicine(all)