Trifluoroacetic acid-mediated facile transformation of 2-C-hydroxymethyl-d-glycals to chiral pyrano[2,3-b]benzopyrans

Treatment of 2-C-hydroxymethyl-d-glycals with phenols in trifluoroacetic acid at ambient temperature leads to an extremely facile transformation affording chiral pyrano[2,3-b]benzopyrans in high yields.     

Influence of ultraviolet radiation on spore liberation in marine macroalgae Ulva fasciata (Ulvales,Chlorophyceae) and Gracilaria corticata (Gracilariales,Rhodophyceae)

The effect of ultraviolet‐B (UV‐B) and UV‐A radiation on spore liberation in the intertidal marine macroalgae Ulva fasciata Delile (Chlorophyceae) and Gracilaria corticata J.Agardh (Rhodophyceae) was investigated. The two algae were exposed to UV‐A and UV‐B radiation separately for 10, 20, 30, 45 and 60 min and percentage inhibition of spore liberation was determined in controlled laboratory conditions. The spore liberation period in UV treated algae was extended for 4 days in U. fasciata and 9 days in G. corticata. UV‐B radiation inhibited spore liberation as much as 76.6% in U. fasciata and 55.5% in G. corticata at 60 min exposure. A significant positive correlation was observed between percentage inhibition of spore liberation and length of UV‐B exposure in both U. fasciata and in G. corticata. Similarly, UV‐A radiation also inhibited spore liberation as much as 75% in the former and 50% in the latter. There was a significant correlation between inhibition of spore liberation and length of UV‐A exposure in U. fasciata and in G. corticata. Analysis of variance results showed inhibition of spore liberation at 60 min of UV exposure differed significantly with that of other exposure lengths. The present findings reveal that UV‐A radiation also had an impact on spore liberation but to a lesser extent than UV‐B radiation. Thallus thickness and plant location on the shore determines their exposure to UV radiation. High UV impact was seen for U. fasciata growing in the upper parts of the intertidal region with a thin sheet like thallus and high surface area resulting in higher inhibition of spore liberation than in G. corticata.     

Photothermal Characterization of Nanogold Under Conditions of Resonant Excitation and Energy Transfer

We have performed thermal diffusion measurements of nanofluid containing gold and rhodamine 6G dye in various ratios. At certain concentrations, gold is nearly four times more efficient than water in dissipating small temperature fluctuations in a medium, and therefore it will find applications as heat transfer fluids. We have employed dual-beam mode-matched thermal lens technique for the present investigation. It is a sensitive technique in measuring photothermal parameters because of the use of a low-power, stabilized laser source as the probe. We also present the results of fluorescence measurements of the dye in the nanogold environment.     

Localization of the PE methylation pathway and SR-BI to the canalicular membrane: evidence for apical PC biosynthesis that may promote biliary excretion of phospholipid and cholesterol

To better understand the regulation of biliary phospholipid and cholesterol excretion, canalicular membranes were isolated from the livers of C57BL/6J mice and abundant proteins separated by SDS-PAGE and identified by matrix-assisted laser desorption/ionization mass spectrometry. A prominent protein revealed by this analysis was betaine homocysteine methyltransferase (BHMT). This enzyme catalyzes the first step in a three-enzyme pathway that promotes the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC). Immunoblotting confirmed the presence of BHMT on the canalicular membrane, failed to reveal the presence of the second enzyme in this pathway, methionine adenosyltransferase, and localized the third enzyme of the pathway, PE N-methyltransferase (PEMT). Furthermore, immunfluorescence microscopy unambiguously confirmed the localization of PEMT to the canalicular membrane. These findings indicate that a local mechanism exists in or around hepatocyte canalicular membranes to promote phosphatidylethnolamine methylation and PC biosynthesis. Finally, immunoblotting revealed the presence and immunofluorescence microscopy unambiguously localized the scavenger receptor class B type I (SR-BI) to the canalicular membrane. Therefore, SR-BI, which is known to play a role in cholesterol uptake at the hepatocyte basolateral membrane, may also be involved in biliary cholesterol excretion. Based on these findings, a model is proposed in which local canalicular membrane PC biosynthesis in concert with the phospholipid transporter mdr2 and SR-BI, promotes the excretion of phospholipid and cholesterol into the bile.     

Substrate specificities of rat oatp1 and ntcp: implications for hepatic organic anion uptake

Transport of a series of 3H-radiolabeled C23, C24, and C27 bile acid derivatives was compared and contrasted in HeLa cell lines stably transfected with rat Na+/taurocholate cotransporting polypeptide (ntcp) or organic anion transporting polypeptide 1 (oatp1) in which expression was under regulation of a zinc-inducible promoter. Similar uptake patterns were observed for both ntcp and oatp1, except that unconjugated hyodeoxycholate was a substrate of oatp1 but not ntcp. Conjugated bile acids were transported better than nonconjugated bile acids, and the configuration of the hydroxyl groups (alpha or beta) had little influence on uptake. Although cholic and 23 norcholic acids were transported by ntcp and oatp1, other unconjugated bile acids (chenodeoxycholic, ursodeoxycholic) were not. In contrast to ntcp, oatp1-mediated uptake of the trihydroxy bile acids taurocholate and glycocholate was four- to eightfold below that of the corresponding dihydroxy conjugates. Ntcp mediated high affinity, sodium-dependent transport of [35S]sulfobromophthalein with a Km similar to that of oatp1-mediated transport of [35S]sulfobromophthalein (Km = 3.7 vs. 3.3 muM, respectively). In addition, for both transporters, uptake of sulfobromophthalein and taurocholic acid showed mutual competitive inhibition. These results indicate that the substrate specificity of ntcp is considerably broader than previously suspected and caution the extrapolation of transport data obtained in vitro to physiological function in vivo.     

Design,synthesis and evaluation of inhibitor of apoptosis protein (IAP) antagonists that are highly selective for the BIR2 domain of XIAP

We recently reported the systematic ligand-based rational design and synthesis of monovalent Smac mimetics that bind preferentially to the BIR2 domain of the anti-apoptotic protein XIAP. Expanded structure–activity relationship (SAR) studies around these peptidomimetics led to compounds with significantly improved selectivity (>60-fold) for the BIR2 domain versus the BIR3 domain of XIAP. The potent and highly selective IAP antagonist 8q (ML183) sensitized TRAIL-resistant prostate cancer cells to apoptotic cell death, highlighting the merit of this probe compound as a valuable tool to investigate the biology of XIAP.