Structural, Biochemical, and Computational Characterization of Sulfamides as Bimetallic Peptidase Inhibitors.

The sulfonamide function is used extensively as a general building block in various inhibitory scaffolds and, more specifically, as a zinc-binding group (ZBG) of metalloenzyme inhibitors. Here, we provide biochemical, structural, and computational characterization of a metallopeptidase in complex with inhibitors, where the mono- and bisubstituted sulfamide functions are designed to directly engage zinc ions of a bimetallic enzyme site. Structural data showed that while monosubstituted sulfamides coordinate active-site zinc ions via the free negatively charged amino group in a canonical manner, their bisubstituted counterparts adopt an atypical binding pattern divergent from expected positioning of corresponding tetrahedral reaction intermediates. Accompanying quantum mechanics calculations revealed that electroneutrality of the sulfamide function is a major factor contributing to the markedly lower potency of bisubstituted compounds by considerably lowering their interaction energy with the enzyme. Overall, while bisubstituted uncharged sulfamide functions can bolster favorable pharmacological properties of a given inhibitor, their use as ZBGs in metalloenzyme inhibitors might be less advantageous due to their suboptimal metal-ligand properties.

Potential clinical application of anti-Müllerian hormone testing in radioiodine treatment of thyroid carcinoma.

Differentiated thyroid cancer is the most common endocrinological malignancy. Radioiodine treatment has a clear benefit in locally aggressive and metastatic cancers. There are discussions about long-term and acute adverse events.Anti-Müllerian hormone is regarded as the best endocrine marker for evaluating the physiological loss of oocytes in healthy women with regard to age. The impact of radioiodine treatment on anti-Müllerian hormone levels has been more significantly reported in patients over 35 years of age. About reproductive dysfunction, calculations of individual absorbed doses of radioiodine in ovaries after thyroid cancer therapy have not been performed yet. The aim of our ongoing prospective study is to determine serum anti-Müllerian hormone to estimate ovarian reserve for premenopausal women treated with radioiodine and to compare anti-Müllerian hormone levels before and after radioiodine treatment. Predicting radioiodine side effects by evaluating a simple serum biomarker may help to select an appropriate treatment strategy for young women planning pregnancy, specifically in the assessment of ovarian reserve and premature ovarian failure with early onset of menopause.