Carbohydrate Mimicking Peptides as Inhibitors of Angiogenesis and Metastasis
Annual rept. 1 Jun 96-31 May 97
WISTAR INST OF ANATOMY AND BIOLOGY PHILADELPHIA PA
Pagination or Media Count:
E-selectin is an inducible cell adhesion molecule which mediates rolling of neutrophils as well as adhesion of carcinoma cells to endothelium. Inhibition of selectin-mediated interaction is a possible means for controlling inflammation induced diseases and metastatic spread. The purpose of these studies is to identify peptide forms mimicking Lewis X LeX, sialyl-Lewis X SA-LeX, sialyl-Lea SA-Lea, and Lewis Y LeY carbohydrate structures to disrupt lectin-ligand interactions and evaluate their properties to block adenocarcinoma cell adhesion to endothelial cells and tumor metastasis in vitro and in vivo. We used recombinant peptide library to identify novel ligands for E-selectin. We have identified five dodeca peptides mimicking SA-Lea carbohydrate, which is one of the E-selectin ligands, via means of random peptide library screening using SA-Lea-specific monoclonal antibody MAb NS 19-9. Peptides with the highest binding affinity for the MAb will be synthesized and characterized for its anti-metastatic activity using JC murine breast and H-59 lung carcinoma cells in metastatic model in vivo.
- Anatomy and Physiology
- Medicine and Medical Research