Solution behavior of leuprolide acetate, an LHRH agonist, as determined by circular dichroism spectroscopy

Leuprolide acetate, a potent agonist of luteinizing hormone-releasing hormone (LHRH), was found to display little or no secondary structure in aqueous solution as determined by circular dichroism (CD) spectroscopy. However, upon addition of trifluoroethanol, CD spectra consistent with type II β-turn structures were observed. CD spectroscopy was also employed to evaluate the aggregation of leuprolide in solution. In aqueous solution, leuprolide does not readily aggregate. However, in ethanol/water mixtures, concentration- and temperature-dependent aggregation was observed. This demonstrates that CD spectroscopy can be an effective analytical tool for assessing not only the structure of peptides, but also detecting peptide aggregation.