Modification of cloned brain Na+ channels by batrachotoxin

The effects of batrachotoxin (BTX) on cloned alpha-subunit Na+ channels were examined in CHO-K1 cells (a chinese hamster ovary cell line) transfected with rat brain NaIIA cDNA. Under whole-cell patch clamp conditions, BTX shifted the voltage dependence of the activation process by about 45 mV towards the hyperpolarizing direction and eliminated the inactivating phase of Na+ currents. Repetitive depolarizations greatly facilitated the binding of BTX with NaIIA channels while the membrane was held at -100 mV. In chloramine-T-pretreated cells, the association rate of BTX binding with the NaIIA channel was 6.5-fold faster than that in untreated cells. The estimated association rate constant for BTX binding with the open form of NaIIA channel was 1.11 x 10(6) mol-1.s-1 at room temperature. BTX-modified NaIIA channels were blocked by tetrodotoxin (TTX) in a complicated manner. First, the TTX binding to the closed state of BTX-modified NaIIA channels was not voltage dependent. The KD value of TTX was measured at 8.9 nM, which was similar to that of unmodified channels (KD = 14.2 nM). Second, the block of the open state of BTX-modified NaIIA channels by TTX was voltage dependent; depolarization reduced the potency of TTX block between -20 mV to +50 mV. Below -30 mV, the TTX affinity began to level off, probably because of the increased presence of the closed state. Unexpectedly, steady-state inactivation of BTX-modified NaIIA channels was minimal as measured by the two-pulse protocol, a phenomenon distinctly different from that found in GH3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

TAK-603 selectively suppresses Th1-type cytokine production and inhibits the progression of adjuvant arthritis

Lipopeptides carrying a farnesyl thioether or a palmitic acid thioester and a farnesyl thioether were prepared from S-farnesyl cysteine methyl ester by N-terminal extension of the peptide chain employing the base labile Fmoc blocking group of the palladium(0) sensitive Aloc urethane. By means of this technique a lipohexapeptide representing the completely functionalized, i.e. palmitoylated and farnesylated C-terminus of the human N-Ras protein, was prepared. If acid labile blocking functions like the Boc group were used, upon deprotection an undesired addition of the acid to the double bonds of the farnesyl residue occurred. Therefore, acid labile blocking groups should not be employed in the synthesis of farnesylated lipopeptides. The lipopeptide methyl esters which carry only a farnesyl group do not inhibit protein farnesyl transferase, whereas palmitoylated peptides are weak inhibitors of this enzyme.     

Compression molding and melt‐spinning of the blends of poly(lactic acid) and poly(butylene succinate‐co‐adipate)

Poly(lactic acid) (PLA) is a biobased polymer made from biomass having high mechanical properties for engineering materials applications. However, PLA has certain limited properties such as its brittleness and low heat distortion temperature. Thus, the aim of this study is to improve toughness of PLA by blending with poly(butylene succinate‐co‐adipate) (PBSA), the biodegradable polymer having high toughness. Polymer blends of PLA and PBSA were prepared using a twin screw extruder. The melt rheology and the thermal property of the blends were examined. Further the blends were fabricated into compression molded parts and melt‐spun fiber and were subjected to tensile and impact tests. When the PBSA content was low, PBSA phase was finely dispersed in the PLA matrix. On the other hand, when the PBSA content was high, this minor phase dispersed as a large droplet. Mechanical properties of the compression molded parts were affected by the dispersion state of PBSA minor component in PLA matrix. Impact strength of the compression molded parts was also improved by the addition of soft PBSA. The improvement was pronounced when the PBSA phase was finely dispersed in PLA matrix. However, the mechanical property of the blend fibers was affected by the postdrawing condition as well as the PBSA content. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41856.