Identification of potent 11mer glucagon-like peptide-1 receptor agonist peptides with novel C-terminal amino acids: Homohomophenylalanine analogs.

Tasir S Haque, Ving G Lee, Douglas Riexinger, Ming Lei, Sarah Malmstrom, Li Xin, Songping Han, Claudio Mapelli, Christopher B Cooper, Ge Zhang, William R Ewing, John Krupinski

Index: Peptides 31(5) , 950-5, (2010)

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Abstract

We report the identification of potent agonists of the Glucagon-Like Peptide-1 Receptor (GLP-1R). These compounds are short, 11 amino acid peptides containing several unnatural amino acids, including (in particular) analogs of homohomophenylalanine (hhPhe) at the C-terminal position. Typically the functional activity of the more potent peptides in this class is in the low picomolar range in an in vitro cAMP assay, with one example demonstrating excellent in vivo activity in an ob/ob mouse model of diabetes.Copyright (c) 2010 Elsevier Inc. All rights reserved.