MEDI 58 |
| The development of peptide-based drugs has recently intensified because of the relative simplicity and high specificity of active agents. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. While the introduction of fluorine in the form of trifluoromethyl groups into small molecule therapeutics often improves druggability, it has not been extensively applied to the modification of peptides and proteins. We report here the design and synthesis of fluorinated analogues of the gut hormone peptide GLP-1. These derivatives were further characterized for their binding affinity to the cognate receptor, signal transduction ability, and proteolytic stability. We demonstrate that incorporation of highly fluorinated amino acids led to the enhanced enzymatic stability and preserved biological activity. These results indicate that fluorinated amino acids could be potentially useful for engineering peptide drug candidates. |
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Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Medicinal Chemistry |