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The mechanism by which cycloheximide and related glutarimide antibiotics inhibit peptide synthesis on reticulocyte ribosomes

AddTime:2019-08-21

Cycloheximide and related glutarimide antibiotics have been shown to affect binding, transfer enzyme II-dependent movement, and release of transfer RNA from the donor site of reticulocyte ribosomes, as well as both the initiation and extension of globin and phenylalanine custom peptide synthesis. They inhibit binding of deacylated tRNAto reticulocyte ribosomes in the absence of transfer enzymes at concentrations similar to those that inhibit peptide initiation. These concentrations are below those required for comparable inhibition of custom peptide synthesis or transfer enzyme II-dependent translocation of peptidyl-tRNA from the acceptor to the donor ribosomal sites and appear to provide the basis for differential inhibition of peptide initiation and extension.
 the subject of this paper which is how to simplify and make more generally usable the 14 C-bicarbonate method of measuring synthetic rate of plasma proteins synthesised by the liver. It shows measurements of the specific radioactivity of the arginine 6-carbon of plasma albumin and plasma fibrinogen obtained about 3 hours after one hour’s intravenous infusion of 0.5 mC 14 C-bicarbonate. Rabbits were injected with 5 mg of cycloheximide per kg of body weight from 1 to 48 hours before the start of the infusion and the specific radioactivities are expressed as fractions of the mean levels we found in untreated healthy control animals. It is seen that the specific radioactivities (SA) of both albumin and fibrinogen arginine-6-C, are reduced almost to zero shortly after the injection, but both show some recovery 6 hours later; albumin SA remains unchanged 12 hours later but by this time fibrinogen arginine-6-C SA has rebounded to more than twice its initial levels; by 24 hours albumin arginine-6-C SA has returned to initial levels while fibrinogen arginine-6-C has fallen to 1.5 times initial levels; and by 48 hours both albumin arginine-6-C and fibrinogen arginine-6-C SA are near initial levels. This is a rather remarkable contrast in the responses of two different liver-synthesised plasma proteins to an agent that blocks ribosomal translation of mRNA 1,2 . We should like to be able to interpret such results in terms of the underlying albumin and fibrinogen synthesis.
custom peptide synthesis
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