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Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that phenocopied genetic STK33 perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound. [ABSTRACT FROM AUTHOR]

Copper nanoparticle-based catalysts have been extensively applied in industry, but the nanoparticles tend to sinter into larger ones in the chemical atmospheres, which is detrimental to catalyst performance. In this work, we used dealuminated Beta zeolite to support copper nanoparticles (Cu/Beta-deAl) and showed that these particles become smaller in methanol vapor at 200°C, decreasing from ~5.6 to ~2.4 nanometers in diameter, which is opposite to the general sintering phenomenon. A reverse ripening process was discovered, whereby migratable copper sites activated by methanol were trapped by silanol nests and the copper species in the nests acted as new nucleation sites for the formation of small nanoparticles. This feature reversed the general sintering channel, resulting in robust catalysts for dimethyl oxalate hydrogenation performed with supported copper nanoparticles for use in industry. [ABSTRACT FROM AUTHOR]

The article offers information on the structural basis of sugar recognition by insect sweet taste receptors, focusing on Drosophila sugar receptors GR43a and GR64a. Topics include the formation of sugar-gated cation channels by GR43a and GR64a; the structural features of these receptors; and the mechanism of sugar binding and channel opening.