Template Based Design of Anti-Metastatic Drugs from the Active Conformation of Laminin Peptide II.
Abstract
The major advances which have been made encompass work elucidating the structure of the ligand binding domain of the 67 kDa LBP. Phage display studies indicated that three sequence domains in the C-terminal domain of the LBP likely interact with peptide 11. NMR studies of the ligand binding domain of the LBP require that the domain be expressed in a recombinant bacterial system. We have accomplished this for the full length protein and the ligand binding domain. In both cases, the E. coli strain expresses large amounts of protein which is readily purified and refolded. Synthesis of candidate 16, which was designed by an early run of the INVENTON program, is essentially complete, and will shortly be investigated for its bioactivity. Refinement of the INVENTON input will soon be undertaken to incorporate new data on the orientation of required amino acid sidechains in peptide 11. Because initial experiments indicated that the 67 kDa LBP could facilitate dimerization of peptide 11 analogs, we compared the bioactivity of peptide 11, a non oxidizable analog of peptide 11 and peptide 11 dimer. The most active species was found to be the dimer with the Acm protected monomer being the least active.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1999
- Accession Number
- ADA363651
Entities
Organizations
- Montana State University