Carbohydrate Mimicking Peptides as Inhibitors of Angiogenesis and Metastasis
Final rept. 1 Jun 96-31 May 99
PENNSYLVANIA UNIV PHILADELPHIA WISTAR INST
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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.
- Medicine and Medical Research