Hexanoylation of a VPAC2 receptor-preferring ligand markedly increased its selectivity and potency
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Updated: Aug 25, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
Ingrid Langer1, Françoise Gregoire, Ingrid Nachtergael
1Department of Biochemistry and Nutrition, School of Medicine, Université Libre de Bruxelles, Bât G/E, CP 611, 808 Route de Lennik, B-1070 Bruxelles, Belgium.
Abstract:
We synthesized a VIP analog that combines mutations that decrease the affinity for the VPAC1 receptor but maintain a high affinity for the VPAC2 receptor with an amino-terminal hexanoylation that increases the affinity for the VPAC2 receptor with a limited decrease in the affinity of the VPAC1 receptor. The resulting Hexanoyl[A19,K(27,28)]VIP had the expected properties of a high affinity for the VPAC2 receptor and a low affinity for the VPAC1 receptor and also a low affinity for the PAC1 and secretin receptors. With a 1000-fold preference for the VPAC2 receptor and a IC50 value of binding of 1 nM, this compound is the most potent and the most selective agonist presently described.
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