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Biomedical subjects

M J Leibowitz

Publications and source records attributed to M J Leibowitz.

66 records · Page 4Linked to original sources
PubMed1971

Modification of a specific ribosomal protein catalyzed by leucyl, phenylalanyl-tRNA: protein transferase.

Escherichia coli ribosomes washed with 1 M NH(4)Cl were found to function as acceptor for leucine and phenylalanine in the reaction catalyzed by leucyl, phenylalanyl-tRNA:protein transferase. When isolated subunits were acylated with [(14)C]phenylalanine and reisolated by gradient centrifugation, the recovered 30S particles had a specific radioactivity nearly 30 times that of similarly treated 50S particles. Autoradiography of gels, which contained protein from acylated 30S particles, that had been subjected to electrophoresis in 8 M urea and in sodium dodecyl sulfate, suggested that acceptor activity was largely due to a single protein with a molecular weight of about 12,000. Leucine and phenylalanine residues that had been transferred to ribosomal protein were reactive with fluorodinitrobenzene and were released as leucyl- or phenylalanylarginine after treatment with trypsin. The results indicate that leucyl, phenylalanyl-tRNA: protein transferase catalyzes the addition of these amino acids to an NH(2)-terminal arginine residue of a specific ribosomal protein on the 30S subunit.

Acyltransferases↗
PubMed1971

The effect of nitrogen mustard intoxication on glucose absorption from the small intestine of the rat.

Methyl bis (beta-chlorethyl) amine (HN(2)) was administered as a single intraperitoneal dose to male Sprague-Dawley rats. Animals were given either a median lethal dose and perfused one day after treatment or were given a larger dose and perfused two days after treatment. Intestinal segments were perfused in vivo and samples of effluent were collected and measured for glucose using the glucose oxidase method. Animals treated with the larger dose of HN(2) displayed significant reduction in intestinal dry weight. The average water content of intestinal segments derived from treated animals did not differ significantly from that in controls.Steady-state glucose absorption, obtained from data collected during the last 40 minutes of the perfusion period, was found to be significantly reduced in animals treated with drugs when intestinal absorption for control and treated animals was adjusted for water movement but not for dry intestinal weight and length. However, when glucose absorption was adjusted for dry tissue mass and length as well as for water movement, no significant differences in intestinal glucose absorption between control and treated rats were observed. Alterations can therefore be attributed to loss of intestinal tissue rather than to loss in the ability of the intestinal mass to absorb glucose.

Animals↗
PubMedDate not supplied

Dual-specificity interaction of HIV-1 TAR RNA with Tat peptide-oligonucleotide conjugates.

An oligonucleotide-peptide conjugate, having dual binding capability for a designated RNA, was designed. The peptide portion of the conjugate interacts with a folded domain in the RNA, whereas the oligonucleotide portion hybridizes with a nearby single-stranded region in the RNA. The dual specificity was proven in a model HIV-1 TAR RNA system using an RNase H cleavage assay to assess antisense binding to this RNA. The peptide portion of the conjugate was shown to confer increased specificity on the oligonucleotide.

Amino Acid Sequence↗
PubMedDate not supplied

A polyethylene glycol copolymer for carrying and releasing multiple copies of cysteine-containing peptides.

Two different methods were developed to prepare an adduct of a poly(ethylene glycol)-lysine copolymer with either cysteamine or 1-amino-2-methyl-2-propanethiol. Cysteine-containing peptides could then be disulfide-linked to the thiol groups on the polymer in a facile manner. In the described procedures, a coupling ratio of about 8 peptides/molecule of poly(ethylene glycol)-lysine copolymer (Mw = 27 000) was typically attained. The products were stable at neutral pH, but the peptides could be released from the polymer in a physiologically relevant reducing environment. The release rate was highly dependent on the linker used for forming the disulfide bond. To illustrate the potential biomedical usefulness of this polymer carrier, a Tat peptide-PEG conjugate was shown to inhibit expression of a reporter gene fused to the TAR element of human immunodeficiency virus in a model cell assay.

Biotinylation↗
PubMedDate not supplied

Inhibition of in vitro splicing of a group I intron of Pneumocystis carinii.

Unlike its mammalian hosts, the opportunistic fungal pathogen Pneumocystis carinii harbors group I self-splicing introns in its chromosomal genes encoding rRNA. This difference between pathogen and host suggests that intron splicing is a promising target for chemotherapy. We have found that intron splicing in vitro is inhibited by the anti-Pneumocystis agent pentamidine and by a series of pentamidine analogues, as well as by some aminoglycosides, tetracycline, L-arginine and ethidium bromide. Further studies will be needed to determine if this is the mechanism of action of pentamidine against P. carinii.

Base Sequence↗
PubMedDate not supplied

Comparison of coding and spacer region sequences of chromosomal rRNA-coding genes of two sequevars of Pneumocystis carinii.

Two distinct sequevars, denoted Pc1 and Pc2, of the opportunistic pathogen Pneumocystis carinii have been previously identified based on the sequence of their 26S rRNA genes, the location of group I self-splicing introns and pulsed field electrophoretic patterns of chromosomal DNA. This study shows that the sequences of 16S and 5.8S rRNA genes also vary between these sequevars, and that greater variation was seen in the internal transcribed spacer regions. Polymerase chain reaction and restriction analysis can distinguish between these sequevars.

Animals↗
PubMedDate not supplied

Bidirectional effectors of a group I intron ribozyme from Pneumocystis carinii.

The L-arginine acts stereoselectively on the Pc1.LSU nuclear group I intron of Pneumocystis carinii, competitively inhibiting the first step of the splicing reaction and stimulating the second step. A number of arginine-related compounds are more potent than L-arginine as stimulators and inhibitors. The most potent peptides tested are 10,000 times as effective as L-arginine in inhibiting ribozyme activity, and nearly 400 times as effective as stimulators. This phenomenon indicates that ribozymes, like protein enzymes, can interact with non-substrate low molecular weight compounds, and that non-nucleic acid agents might be developed as drugs acting on RNA targets.

Animals↗