A Novel Serine Protease Target for Prevention of Breast Cancer by a Soy Bean-Derived Inhibitor

Abstract

In year 2 of our studies of the inhibitory interaction between matriptase and HAl1, and between matriptase and BBI, we have built a 3-D structure of the protease domain of matriptase, based on the homology modeling using the X-ray structure of human thrombin as template. This modeled matriptase structure was used in a structure-based screening of inhibitors. Screening from the NCI small compounds database, we have developed bis-benzamidines as potent matriptase inhibitors. We have also found that, in addition to HAl1, a recently discovered natural trypsin inhibitor, SFTI, from sunflower seed, inhibits matriptase. We have found that in non-transformed mammary epithelial cells, the activated matriptase can be stimulated by lipid phosphates; the activated matriptase is then quickly bound to HAl1, and shed into media.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2001
Accession Number
ADA395463

Entities

People

  • Robert B. Dickson

Organizations

  • Georgetown University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Albumins
  • Amino Acids
  • Biomedical And Dental Materials
  • Biomedical Research
  • Blood
  • Breast Cancer
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Epithelial Cells
  • Liquid Chromatography
  • Molecular Dynamics
  • Neoplasms
  • Organic Chemistry
  • Peptide Growth Factors
  • Peptides
  • Proteins

Fields of Study

  • Chemistry

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biochemistry