Potent Dipeptide Inhibitors of the pp60c-src SH2 Domain
| Autor: | Renae M. Crosby, Christopher Mohr, Daniel D. Sternbach, Steven R. Jordan, Krystal J. Alligood, Paul L. Feldman, Paul S. Charifson, George F. Dorsey, Conrad W. Hummel, Judd Berman, Lisa M. Shewchuk, Gregory J. Pacofsky, Marc Rodriguez, Tona M. Gilmer, Karen Lackey |
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| Rok vydání: | 1998 |
| Předmět: |
Models
Molecular chemistry.chemical_classification Dipeptide Molecular model Chemistry Stereochemistry Phosphopeptide Proto-Oncogene Proteins pp60(c-src) Molecular Conformation Enzyme-Linked Immunosorbent Assay Peptide Dipeptides Crystallography X-Ray Ligands SH2 domain Ligand (biochemistry) src Homology Domains Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Peptide synthesis Humans Molecular Medicine Structure–activity relationship Enzyme Inhibitors |
| Zdroj: | Journal of Medicinal Chemistry. 41:1894-1908 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | The design, synthesis, and evaluation of dipeptide analogues as ligands for the pp60c-src SH2 domain are described. The critical binding interactions between Ac-Tyr-Glu-N(n-C5H11)2 (2) and the protein are established and form the basis for our structure-based drug design efforts. The effects of changes in both the C-terminal (11-27) and N-terminal (51-69) portions of the dipeptide are explored. Analogues with reduced overall charge (92-95) are also investigated. We demonstrate the feasibility of pairing structurally diverse subunits in a modest dipeptide framework with the goal of increasing the druglike attributes without sacrificing binding affinity. |
| Databáze: | OpenAIRE |
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