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Influence of selective fluorination on the biological activity and proteolytic stability of glucagon-like peptide-1.

ABSTRACT: The relative simplicity and high specificity of peptide therapeutics has fueled recent interest. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. We report here the design, synthesis, and characterization of fluorinated analogues of the gut hormone peptide, GLP-1. Overall, fluorinated GLP-1 analogues displayed higher proteolytic stability with simultaneous retention of biological activity (efficacy). Fluorinated amino acids are useful for engineering peptide drug candidates and probing ligand-receptor interactions.

SUBMITTER: Meng H

PROVIDER: S-EPMC2645917 | biostudies-other | 2008 Nov

REPOSITORIES: biostudies-other

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Influence of selective fluorination on the biological activity and proteolytic stability of glucagon-like peptide-1.

Meng He H Krishnaji Subrahmanian Tarakkad ST Beinborn Martin M Kumar Krishna K

Journal of medicinal chemistry 20081101 22

The relative simplicity and high specificity of peptide therapeutics has fueled recent interest. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. We report here the design, synthesis, and characterization of fluorinated analogues of the gut hormone peptide, GLP-1. Overall, fluorinated GLP-1 analogues displayed higher proteolytic stability with simultaneous retention of biological activity (efficacy). Fluorinated amino acids are useful for en ...[more]

PMID: 18950150

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