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Characterization of the solution conformations of leuprolide acetate
Authors:J D Meyer  M C Manning  D G Vander Velde
Abstract: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 β‐turns in water, a nascent helix in TFE/water at low pH, and a high population β‐turn in TFE/water at slightly acidic pH. The pH‐related conformational change in TFE/water is attributed to the pKa of the acetate counterion, not to ionizable groups on the peptide. None of these conformations are in exact agreement with previous computational predictions.
Keywords:circular dichroism  leuprolide  NMR  peptide conformation in solution  trifluoroethanol
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