From childhood migraine headache to pheochromocytoma.

Pheochromocytoma may have multiple clinical manifestations including paroxysmal hypertension, tachycardia, sweating, nausea, and headache (Phillips et al., 2002). Migraine has some of the manifestations seen with pheochromocytoma. We describe a patient who had a history of migraine headaches since childhood and was found to have pheochromocytoma. Resection of her tumor significantly improved her headache. The diagnoses of pheochromocytoma subsequently lead to diagnosing her with medullary thyroid cancer (MTC) and multiple endocrine neoplasia type 2A (MEN-2A).

Predicted and trifluoroethanol-induced alpha-helicity of polypeptides.

The alpha-helix stabilizing solvent 2,2,2-trifluoroethanol (TFE) is frequently used as a medium for determining the average alpha-helicity of polypeptides by CD spectroscopy. CD spectra measured in solutions containing 10, 15, 20, 50, and 90% (vol/vol) TFE are presented for 5 peptides that were selected to demonstrate possible variations in the effect of TFE concentration on the secondary structure. The analysis is extended to 6 further peptides whose CD spectra as measured in TFE are documented in the literature. The observed alpha-helicity at a high TFE concentration is compared with the alpha-helicity determined by a structure prediction method that combines conformational filtering [S. Vajda, (1993) Journal of Molecular Biology, Vol. 229, pp. 125-145], and a Monte Carlo simulation [J. Figge et al. (1993) Protein Science, Vol. 2, pp. 155-164]. For the set of 11 peptides we find a correlation of 0.84 between the predicted [theta]222 values and the corresponding values observed by CD spectroscopy in a high concentration of TFE (p < 0.01). Although we generally find a good correlation at high TFE concentration between observed and predicted alpha-helicity, there are several peptides that do not follow the predicted behavior. An analysis of the TFE titration curves in one such case revealed that TFE can induce a sharp transition from a partial beta-sheet conformation to an alpha-helical conformation as the TFE concentration is increased above a critical value.

Environmental effects on the folding of functional peptide segments from steroid hormone receptors.

Recent improvements in circular dichroism (CD) instrumentation now allow investigators to obtain highly reliable and reproducible CD spectra in the far-UV range to near 180 nm. These advances, coupled with new computer software for spectral interpretation, allow accurate calculations of secondary structural content in proteins and polypeptides. CD is particularly reliable for the calculation of alpha-helical content. We have utilized these features to determine the propensity of alpha-helix formation in highly purified synthetic peptides corresponding to segments from proteins. We obtain CD spectra of the peptides in 90% 2,2,2-trifluoroethanol (90% TFE; an alpha-helix promoting solvent) and in 2 mM sodium dodecyl sulfate (2 mM SDS; a beta-sheet promoting solvent) to assess helix stability in these different chemical environments. Using this methodology, we demonstrate that a peptide corresponding to a biologically active segment of the human estrogen receptor forms a stable alpha-helix in both environments. In contrast, peptide segments of equal length from other steroid receptors are alpha-helical in TFE but not in 2 mM SDS. These results show that the conformation of a peptide is a function of both its amino acid sequence and the local chemical environment.