Antibiotics puromycin

One type of fatty liver that has been smdied extensively in rats is due to a deficiency of choline, which has therefore been called a lipotropic factor. The antibiotic puromycin, ethionine (a-amino-y-mercaptobu-tyric acid), carbon tetrachloride, chloroform, phosphorus, lead, and arsenic all cause fatty liver and a marked reduction in concentration of VLDL in rats. Choline will not protect the organism against these agents but appears to aid in recovery. The action of carbon tetrachloride probably involves formation of free radicals... 

Figure 38-11. The comparative structures of the antibiotic puromycin (fop) and the 3 terminal portion of tyrosinyl-tRNA (bottom).

The peptidyltransferase site. The position was located by binding of derivatives of the antibiotic puromycin (Fig. 29-13). An arylazide derivative of puromycin was photochemically linked (Eq. 23-27) to proteins L23, L18/22, and L15 immunoelectron microscopy, using antibodies to the -dimethyl-adenosine of puromycin,165 166 located the binding site adjacent to the central protuberance between the 50S subunit and 30S subunit near S14.5 4-Thio-dT-p-C-p-puromycin was photochemically crosslinked to G2553... 

Figure 29-13 (A) Structure of expected intermediate with tetrahedral C-atom in peptidyltransferase reaction with a tRNA, with a minihelix analog, or with the antibiotic puromycin. (B) Transition-state (or bisubstrate) analog formed with puromycin and a mimic of the CCA end of a tRNA. See Box 29-B.

Baker s original work concerned the synthesis of 3-amino-3-deoxy-D-ribose, a component residue of the antibiotic puromycin.29 Two independent syntheses were achieved, starting from L-arabinose and D-xylose, respectively. The main steps in the reaction schemes are outlined in the following reaction sequences. 

Immune complexes Aminoglycoside antibiotics Puromycin aminonucleoside Adriamycin Penicillamine... 

The antibiotic puromycin (18), produced by Streptomyces alhoniger, on alcoholysis yields 6-(dimethylamino)purine, 0-methyl-L-tyrosine, and... 

The behavior of the antibiotic puromycin (96) and some of its derivatives upon electron impact has been investigated (97). The mass spectrum of the corresponding 3-amino-3-deoxy nucleoside 67, which was investigated as a model substance, is shown in Figure 25. The incorporation of rearranged hydrogens in the base portion (B - - 1 and B -1- 2)... 

Lacalte ELA, Teicero JA, Jimenez A. Cloning of the complete biosynthetic gene cluster fiw an aminonucleoside antibiotic, puromycin, and its regulated expression in heterologous hosts. EMBOJ 1992 11 785-792. 

The daunosaminyl (3-amino-2,3,6-trideoxy-L-/) xo-hexopyranosyl) analogue of the antibiotic puromycin and -daunosaminyl derivatives of adenine, thymine, and cytosine have been synthesized. " For example, 9-P-daunosaminyladenine was prepared by condensing 3-lV,4-0-bis(trifluoroacetyl)-a-daunosaminyl chloride with lV -benzoyl-9-chloromercuriadenine in refluxing xylene, or with IV -benz-oyladenine in dichloromethane at room temperature in the presence of a molecular sieve, and removal of the protecting groups from the product. 

The action of ammonia or amines on the epoxy sugars results in ring opening with the formation of aminodeoxy sugars or their derivatives. An interesting example is found in the conversion of D-xylose to 3-amino-3-deoxy-D-ribose, a structural component of the antibiotic puromycin (80). The transformation (see formulas on p. 392) is remarkable in that derivatives of all four D-aldopentoses are involved. 

A pep-tRNA or an aa-tRNA is considered bound to the P site if it reacts with the antibiotic puromycin. The structure of puromycin resembles the aminoacyl end of an aa-tRNA, and the ribosome treats it as an acceptor in peptide bond formation. One rarely obtains a puromycin reactivity of 100%. Assumptions are often made about the binding sites of the tRNAs that do not react with puromycin, but the actual binding sites are unknown. The puromycin-unreactive tRNAs may be binding to a non-P site, or to a P site on an inactive ribosome, or may simply... 

It is possible to measure the peptidyl transferase activity of the large subunit in the absence of mRNA by using the antibiotic puromycin, which resembles the 3 -terminal region of Phe-tRNA in structure, as an artificial acceptor to form methionyl puromycin from Met-tRNAf. 

The antibiotic puromycin has a structure very similar to the terminal adenylic acid of tRNA (Fig. 2.2). However, the primary 5 -hydroxyl of... 

Fig. 2.2. Structure of the antibiotic puromycin. Puromycin interrupts the synthesis of the protein chain by mimicing an aminoacyl-tRNA complex, binding to the ribosome, attacking a peptidyl-tRNA (at the P site) with its amino function, but then not undergoing attack by an aminoacyl-tRNA, hence terminating the synthesis. In the upper right corner is shown the adenylic acid terminus of tRNA.

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