Single‐Walled Carbon Nanotubes as Scaffolds to Concentrate DNA for the Study of DNA–Protein Interactions

Genomic DNA in bacteria exists in a condensed state, which exhibits different biochemical and biophysical properties from a dilute solution. DNA was concentrated on streptavidin‐covered single‐walled carbon nanotubes (Strep ? SWNTs) through biotin–streptavidin interactions. We reasoned that confining DNA within a defined space through mechanical constraints, rather than by manipulating buffer conditions, would more closely resemble physiological conditions. By ensuring a high streptavidin loading on SWNTs of about 1 streptavidin tetramer per 4 nm of SWNT, we were able to achieve dense DNA binding. DNA is bound to Strep ? SWNTs at a tunable density and up to as high as 0.5 mg mL^?1 in solution and 29 mg mL^?1 on a 2D surface. This platform allows us to observe the aggregation behavior of DNA at high concentrations and the counteracting effects of HU protein (a histone‐like protein from Escherichia coli strain U93) on the DNA aggregates. This provides an in vitro model for studying DNA–DNA and DNA–protein interactions at a high DNA concentration.     

Synthesis and pharmacological evaluation of new progesterone esters as 5alpha-reductase inhibitors

In this study we report the synthesis and pharmacological evaluation of four new progesterone derivatives; 17alpha-hydroxy-16beta-methylpregna-4,6-diene-3,20-dione 12, 17alpha-cyclopropylcarbonyloxy-16beta-methylpregna-4,6-diene-3,20-dione 13, 17alpha-cyclobutylcarbonyloxy-16beta-methylpregna-4,6-diene-3,20-dione 14, 17alpha-acetoxy-16beta-methylpregna-4,6-diene-3,20-dione 15 and the pregnatriene compound 17alpha-cyclobutylcarbonyloxy-16beta-methylpregna-1,4,6-triene-3,20-dione 16. The pharmacological effect of these compounds was determined in vivo as well as in vitro. The evaluation in vivo was carried out on gonadectomized male hamsters that were injected subcutaneously daily with testosterone (T) and/or finasteride, or with the novel compounds. At the end of the treatments the animals were sacrificed and the prostates were weighed. It was observed that when testosterone (T) and finasteride or compounds 12-16 were injected together, the weight of the prostate decreased significantly as compared to that of the testosterone-treated animals. The 5alpha-reductase inhibitory activity was evaluated in vitro using human prostate homogenates. These experiments showed the following IC50 values: compound 12 (alcohol at C-17) 1.2 x 10(-6) M, 13 (cyclopropyl substituent at C-17) 7.9 x 10(-10) M, 14 (cyclobutyl substituent) 3.2 x 10(-8) M, 15 (acetoxy substituent) 6.3 x 10(-11) M and 16 (cyclobutyl substituent) 3.9 x 10(-6) M. It is evident from these data that when the size of the substituent at C-17 is decreased, the 5alpha-reductase inhibitory activity increases. Apparently, in this biological model, the 5alpha-reductase inhibitory activity depends upon the steric effect of the substituent at C-17. However, the free alcohol 12 showed much lower 5alpha-reductase inhibitory activity.