Structure-activity analysis of the growth hormone Secretagogue GHRP-6 by α- and β-amino γ-lactam positional scanning

Boutard, N., Jamieson, A. G. , Ong, H. and Lubell, W. D. (2010) Structure-activity analysis of the growth hormone Secretagogue GHRP-6 by α- and β-amino γ-lactam positional scanning. Chemical Biology and Drug Design, 75(1), pp. 40-50. (doi:10.1111/j.1747-0285.2009.00913.x)

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Abstract

Incorporation of amino lactams into biologically active peptides restricts conformational mobility and may enhance selectivity and increase potency. α- and β-amino γ-lactams (Agl and Bgl), in both S and R configurations, were introduced into the growth hormone secretagogue GHRP-6 using a Fmoc-compatible solid-phase protocol relying on N-alkylation with five- and six-membered cyclic sulfamidates, followed by lactam annulation under microwave heating. Using this protocol in conjunction with IRORI KanTM techniques furnished eleven new GHRP-6 analogs, and their binding affinity IC50 values on both the growth hormone secretagogue receptor 1a (GHS-R1a) and CD36 receptors are herein reported. The results indicate that selectivity towards one receptor or the other can be modulated by lactam substitution, typically at the Ala3 and the d-Phe5 positions.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jamieson, Dr Andrew
Authors: Boutard, N., Jamieson, A. G., Ong, H., and Lubell, W. D.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Chemical Biology and Drug Design
Publisher:Wiley
ISSN:1747-0277
ISSN (Online):1747-0285
Published Online:30 November 2009

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