Synthesis, conformational analysis and CB1 binding affinity of hairpin-like anandamide pseudopeptide mimetics

Journal of Peptide Science : an Official Publication of the European Peptide Society
Maria Di MarzoLuigi Gomez-Paloma

Abstract

We have designed, synthesized and evaluated the CB(1) binding affinity of a number of new conformationally restricted lipopeptides (1-17). All of them present some of the AEA key structural elements incorporated in a hairpinlike peptide framework. Among them, compounds 1-3 and 8 showed CB(1) affinities in competitive binding assays with K(i) values in the micromolar range (K(i) of AEA = 0.8 microM in the same assay). The remaining pseudopeptides showed little binding to the CB(1) receptor (with K(i) values >or= 50 microM). Conformational analysis on two representative compounds, performed by a combination of NMR studies, restrained molecular dynamics and QM calculations, allowed us to shed light on the structure-activity relationships (SAR), pointing to a correlation between the predominance of the hairpin-like structural motif and the CB(1) binding affinity. In a more general context, the present study may also prove useful in gaining additional insight into the biological relevance of the various AEA conformations.

References

Nov 1, 1991·Pharmacology, Biochemistry, and Behavior·B R MartinS J Ward
Jan 19, 1996·Journal of Medicinal Chemistry·B F ThomasR K Razdan
Oct 25, 1996·Journal of Medicinal Chemistry·A D KhanolkarA Makriyannis
Feb 7, 1997·The Journal of Biological Chemistry·T BisognoV Di Marzo
Feb 28, 1997·Journal of Medicinal Chemistry·T SheskinR Mechoulam
Jan 1, 1997·Advances in Experimental Medicine and Biology·V Di MarzoS Maurelli
Aug 26, 1999·Life Sciences·A D Khanolkar, A Makriyannis
Sep 15, 2004·Magnetic Resonance in Chemistry : MRC·Paola CiminoGiuseppe Bifulco

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Citations

Sep 9, 2008·Medicinal Research Reviews·Lumír Ondrej Hanus
Dec 24, 2014·Life Sciences·F AtivieA Bilkei-Gorzo
Jul 1, 2019·Archives of Toxicology·Je-Oh LimJong-Choon Kim

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