title: Characterization of the solution conformations of leuprolide acetate.
abstract: Leuprolide acetate (pGlu-His-Trp-Ser-Tyr-d-Leu-Leu-Arg-Pro-NHEt), a potent LHRH agonist in wide clinical use, was characterized conformationally by NMR and circular dichroism. It displayed quite different preferred conformations under different solution conditions: two low population beta-turns in water, a nascent helix in TFE/water at low pH, and a high population beta-turn in TFE/water at slightly acidic pH. The pH-related conformational change in TFE/water is attributed to the pK(a) of the acetate counterion, not to ionizable groups on the peptide. None of these conformations are in exact agreement with previous computational predictions.
authors.affiliation: Center for Pharmaceutical Biotechnology, University of Colorado Health Sciences Center, Denver, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Meyer
authors.forename: M C
authors.initials: MC
authors.lastname: Manning
authors.forename: D G
authors.initials: DG
authors.lastname: Vander Velde
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D016729:Leuprolide / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D012996:Solutions; D013696:Temperature; D014270:Trifluoroethanol / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D012996:Solutions; D014867:Water; D014270:Trifluoroethanol; D016729:Leuprolide