Accession Number:

ADA371263

Title:

Carbohydrate Mimicking Peptides as Inhibitors of Angiogenesis and Metastasis

Descriptive Note:

Final rept. 1 Jun 96-31 May 99

Corporate Author:

PENNSYLVANIA UNIV PHILADELPHIA WISTAR INST

Personal Author(s):

Report Date:

1999-06-01

Pagination or Media Count:

63.0

Abstract:

Sialyl-Lewis a SA-Lea and its structural isomer Sialyl-Lewis X SA-LeX carbohydrates are expressed on leukocytes and carcinoma cells and are E-selectin ligands. A SA-Lea mimicking peptide with the sequence DLWDWFVGKPAG was previously identified by us by screening a combinatorial peptide library using a SA-Lea specific monoclonal antibody MAb NS19-9. In further studies, peptide DLWDWFVGKPAG was identified using peptide array which showed higher MAb binding affinity as compared to the lead peptide. We demonstrated that a peptide mimics of SA-Lea mediate a 30 and 50 inhibition of neutrophil recruitment in acute inflammatory conditions and lung colonization of tumor cells in an in vivo murine tumor model, respectively. Similar effect was achieved in E-selectin deficient mice, where metastases were completely abrogated using our established tumor model.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE