Erythromycin Series. X. Inhibitory Activity of Several New Erythromycin Derivatives in Cell-Free Amino Acid Polymerization Systems

Erythromycin A (I), erythromycin A 9-oxime (11), 9(S)-erythromycylamine (V), and several new derivatives of these compounds, were assayed for their ability to inhibit the poly(A)-directed synthesis of polylysine and the poly(C)-directed synthesis of polyproline in cell-free systems from Escherichia coli. The rate of polypeptide synthesis was inhibited 500/o by concentrations between 0.5 and 1.5 ~tmol · dm-3 of the eight examined compounds, in the following decreasing order of activity: methylsuccinate of V (VI), I, V, II, methylsuccinate of II (111), p-toluenesulfonyl-V (VII), p- acetylamino-benzenesulfonyl-V (VIII), and ethylsuccinate of I (IV). The derivative of VII lacking cladinose (IX) showed lower but still significant activity. Hence, none of the substitutions in the position 9 of the macrolide ring, present in these compounds, impairs the ability of I to bind the prokaryotic ribosome and inhibit its function, which is the basis for antibacterial activity of erythromycines

Nucleases in Yeast Acting on the 3\u27-Terminus of Transfer Ribonucleic Acid

Two enzymes capable of hydrolytic removal of 3\u27-terminal adenosine from specifically labeled tRNA were identified in yeast. One of them was highly purified by chromatography on phosphocellulose. It acts on the 3\u27-terminus of tRNA by removing free adenosine, followed by 2\u27- (or 3\u27-) cytidylic acid; it also hydrolyses dinucleoside monophosphates, viral and ribosomal RNA, but it is inactive against either native or denatured DNA. Hence, the enzyme is a ribonucleate 3\u27-nucleotidohydrolase, and may be identical to previously described »ribosomal« ribonuclease of yeast. The other enzyme is a labile acidic protein, with M. W. around 31000. It removes the 3\u27-terminal adenosine of tRNA as adenosine- 5\u27-monophosphate in a reaction with a pH optimum of 7.2, which is not inhibited by Mgrt. Chemical and photochemical modification of tRNA increases its susceptibility to the enzyme. In conjunction with tRNA adenylyl (cytidylyl) transferase, the enzyme may be responsible for the turnover of 3\u27-terminal adenylic acid in yeast

Catalytic Hydrogenation of Some 2-Acetamidoaldose Derivatives

In earlier work, the double bond in aldohexopyranose derivatives with the grouping C=CNAc2 was shown to be resistant to catalytic reduction. Further examples of this phenomenon are now described. Thus, compounds IV, V, and VI were found to be unaltered by hydrogen in the presence of a palladium catalyst. However, 1,4,6-tri-0-acetyl -2- (N-acetylacetamido) -2,3-dideoxy- a-D- erythro-hex-2-enopyranose (VII) and its D-threo isomer VIII undergo allylic hydrogenolysis of the C-1 acetoxy group with migration of the double bond to the C-1-C-2 position to give IX and X, respectively. The acetamido group does not inhibit the reduction of adjacent double bonds; 2-acetamido-1,4,6-tri-0-acetyl- 2,3-dideoxy-a-o-erythro-hex-2-enopyranose (XIII) and 2-acetamido- 4,6-di-0-acetyl -1-0-benzoyl-2,3-dideoxy-a-o-erythro-hex-2- -enopyranose (XV) are reduced to the same 2-acetamido-4,6-di-O- -acetyl-1,5-anhydro-2,3-dideoxy-o-arabino (or o-ribo)-hexitol (XIV) and 2-acetamido-1,4,6-tri-0-acetyl-2,3-dideoxy-~-D-arabino (or o- ribo)-hexopyranose (XX). Some mechanistic features of these reactions are pointed out. The pattern of selectivity shown in the hydrogenation is discussed and a rationalization of the observed facts is offered

Acid inhibition and peptic ulcer bleeding

Peptic ulcer bleeding is one of the most common emergency situations in medicine. Combined pharmacological and endoscopic therapy together with emerging interventional radiological procedures are successfully treating peptic ulcer disease, reserving surgical procedures for only a small portion of patients unresponsive to 'conventional' therapy. Technological advancement has seen a great improvement in the field of endoscopic treatment in the form of various methods of hemostasis. However, pharmacological therapy with proton pump inhibitors still plays the central role in the peptic ulcer bleeding treatment algorithm