A conformation-preference/potency correlation for GnRH analogs: NMR evidence

• Published in: Bioorganic & medicinal chemistry letters Vol. 1; no. 5; pp. 263 - 266
• Main Authors: Andersen, Niels H., Hammen, Philip K.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 1991
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)81039-8

Unlike natural GnRH (which shows a random flexible conformation with a populated reverse turn at residues 3,4), napharelin adopts (in aqueous media containing hexafluoroisopropanol) a non-random conformation in the region of the putative pharmacophore, a type II' β turn at residues 5→8. Napharelin (unlike native GnRH) yields aqueous NMR data consistent with the formation of a 6–7 reverse turn (the putative bioactive conformation) upon addition of (CF 3) 2CHOH. This structuring is most readily seen in the comparison of NH shift temperature gradients along the backbone and confirmed by sequence specific cross-peaks in the NOESY spectrum