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. 2007 Nov 29;50(24):6126-32.
doi: 10.1021/jm070861j. Epub 2007 Nov 2.

Structure-activity and protraction relationship of long-acting glucagon-like peptide-1 derivatives: importance of fatty acid length, polarity, and bulkiness

Kjeld Madsen  1 , Lotte Bjerre Knudsen, Henrik Agersoe, Per Franklin Nielsen, Henning Thøgersen, Michael Wilken, Nils Langeland Johansen
Affiliations

Structure-activity and protraction relationship of long-acting glucagon-like peptide-1 derivatives: importance of fatty acid length, polarity, and bulkiness

Kjeld Madsen et al. J Med Chem. .

Abstract

We here report a series of derivatives describing the structure-activity relationship around liraglutide, a once-daily human glucagon-like peptide-1 fatty acid derivative, with respect to potency as well as protraction in vivo. The spacer region between the fatty acid and the peptide is mostly important for potency, whereas the fatty acid or fatty acid mimetic is important for both potency and protraction. The length of the fatty acid is the most important parameter for protraction.

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