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Biomedical subjects

T Ojasoo

Publications and source records attributed to T Ojasoo.

45 records · Page 3Linked to original sources
PubMed1978

Unique steroid congeners for receptor studies.

To determine the hormone-dependence of a tumor, it is preferable to use highly specific radiolabeled ligands when available, since often more than one class of steroid hormone receptor is present in the tissue specimen, and interference from classes other than the one under study cannot be readily eliminated. In this study, we describe a simple in vitro system used to define the molecular requirements for a highly specific interaction between a steroid and the receptor corresponding to a single class of hormone. It is based on the use of homogenate or crude 105,000 X g supernatant prepared from the target organs considered as end points in routine biological potency tests and on the use of available radioligands not bound by plasma proteins (tags) to single out the receptors. For each receptor singled out in the target organ cytoplasm, the ability of over 700 molecules to decrease bound radioactivity was compared to that of the natural hormone (relative binding affinity) with the use of a dextran-coated charcoal technique to separate bound from unbound steroid. On the basis of the results on 81 molecules, presented in this study, the effect of various substituents on the affinity and specificity of the natural hormones was determined. Molecules interacting markedly with several receptors were submitted to X-ray crystallography in order to establish whether overlap between the various conformations of the natural hormone and of the test molecule might not partly account for lack of specificity.

Animals↗
PubMed1977

Stability of 70S ribosomes in relation to misreading and antibacterial activity of aminoglycosides.

The anomeric aminoglycosides, RU 21886 and RU 23468, which both have a 2-deoxystreptamine residue, stabilize 70S ribosomes to similar extents at low magnesium ion concentrations. Only RU 21886, however, has marked antibacterial and bactericidal activity and gives rise to a high level of misreading in cell-free protein synthesizing systems. It would thus appear that the ability to stabilize the association of the two ribosomal subunits does not necessarily lead to errors in translation.

Aminoglycosides↗
PubMed1977

Properties of the cytoplasmic progestin-binding protein in the rabbit uterus.

An exchange assay for the measurement of total cytoplasmic progestin binding sites has been developed on rabbit uterine cytosol using the highly potent progestin, R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) labelled to a high specific activity. This compound has several advantages over progesterone: it is not bound by plasma corticosteroid binding globulin; it has high affinity for the progestin receptor; it binds virtually as fast as progesterone to the receptor, but the complex formed dissociated 8 times slower; its binding is not displaced by more than 2% by compounds devoid of progestational activity (estrogens, testosterone, dexamethasone, aldosterone). Bound endogenous progesterone was exchanged by tritiated R 5020 in a time compatible with receptor stability. At 0 C, total exchange of filled sites occurred in less than 4 h; at this temperature the R 5020-receptor complex was stable for at least 28 h. The conformation of the R 5020-receptor complex was investigated in sucrose density gradients under various experimental conditions. Unlike progesterone, it was possible to detect a 7S peak in uterine cytosol obtained from rabbits injected with a tracer dose of [3H]R 5020 1 h prior to sacrifice.

Animals↗
PubMed1976

Paromomycin and dihydrostreptomycin binding to Escherichia coli ribosomes.

Paromomycin binds specifically to a single type of binding site on the 70-S streptomycin-sensitive Escherichia coli ribosome. This site is different from that of dihydrostreptomycin since paromomycin binds to streptomycin-resistant ribosomes and sine dihydrostreptomycin does not compete for paromomycin binding. Paromomycin binding, unlike dihydrostreptomycin binding, is independent of changes in ribosome concentration but influenced by magnesium ion concentration. Moreover, paromomycin does not bind to the 30-S subunit of the streptomycin-sensitive ribosome, except in the presence of dihydrostreptomycin, which probably induces the conformational changes necessary for a paromomycin binding site. This induction does not occur with streptomycin-resistant ribosomes. Neither antibiotic binds to the 50-S subunit. In general, binding of the one antibiotic increases the number of sites available for binding of the other. Both antibiotics exhibit marked non-specific binding at high antibiotic/ribosome ratios. Competition studies have enabled the classification of other aminoglycosides according to their ability to compete for the paromomycin and dihydrostreptomycin binding sites. Derivatives structurally related to paromomycin compete for its binding, the degree of competition being related to antibacterial activity, but do not compete for dihydrostreptomycin binding; they, on the contrary, increase the number of dihydrostreptomycin binding sites. Neither gentamicin nor kanamycin derivatives, which induce a high level of misreading, nor kasugamycin and spectinomycin, which do not induce misreading, compete for paromomycin or dihydrostreptomycin binding sites. Other sites may be involved in the binding of these aminoglycosides and in inducing misreading.

Aminoglycosides↗