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Biomedical subjects

S S Cohen

Publications and source records attributed to S S Cohen.

At least 19 recordsLinked to original sources
PubMed1979

Comparative biochemistry and drug design for infectious disease.

In the past two decades, biochemistry and molecular biology have demonstrated the existence of potentially exploitable biochemical differences between etiologic agents of disease and their hosts. Known differences between organism and host with respect to metabolism and polymer structure point to the detailed characterization of key proteins as the focus for the development of potential inhibitors. In the last decade, the methodology of the isolation, characterization, and inactivation of proteins and enzymes has been advanced. The present scientific and technological base suggests that new efforts toward the development of selective chemotherapeutic agents for infections caused by bacteria, viruses, protozoa, and higher eukaryotes should exploit the known differences in proteins or other specific biopolymers serving crucial structural or metabolic roles in the economy of the parasite.

Anti-Bacterial Agents↗
PubMed1979

Uptake and accumulation of putrescine and its lethality in Anacystis nidulans.

The rate of uptake of putrescine by Anacystis nidulans has been shown to depend on the external pH and the extracellular concentration of putrescine. Accumulation of exogenous putrescine was also proportional to the concentration of putrescine in the medium, suggesting that putrescine uptake was not subject to cellular regulation. An equation was derived to test the hypothesis that putrescine accumulation was due to ion trapping. Comparison of the predicted and observed intracellular concentrations of putrescine under various conditions showed a close correlation in support of the hypothesis of ion trapping. Under conditions leading to cell death (e.g., 150 microM putrescine, pH 9.8), the correlation did not hold as a result of leakage of accumulated putrescine.

Cyanobacteria↗
PubMed1979

Mechanism of toxicity of putrescine in Anacystis nidulans.

Putrescine is lethal to the cyanobacterium Anacystis nidulans at extracellular pH values at which significant concentrations of the nonprotonated diamine rapidly diffuse into the cell and accumulate as the charged form. Although over 98% of the accumulated putrescine is not metabolized, a small fraction is rendered trichloroacetic acid-insoluble, and about 90% of this is bound as putrescinie to proteins and cell structures. Various synthetic functions were studied in the presence of a bacteriostatic (40 microM) and a bacteriocidal (150 microM) concentration of putrescine at pH 9.5. Under lethal conditions, protein synthesis was completely inhibited after 45 min and CO2 fixation after 100 min, whereas nucleic acid synthesis was less affected. Spermidine was lost from the cell and its synthesis was arrested. These functions were much less inhibited at 40 microM putrescine. Ribosomes from putrescine-killed cells were found to be irreversibly dissociated into 30S and 50S subunits. Some putrescine (1-4 molecules) cosedimented with each subunit.

Biological Transport↗
PubMed1978

Erythro-9-(2-hydroxy-3-nonyl)adenine as a specific inhibitor of herpes simplex virus replication in the presence and absence of adenosine analogues.

Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; erythro-9-[3-(hydroxynonyl)]adenine), a reversible inhibitor of adenosine deaminase, significantly inhibits replication of herpes simplex virus (HSV), whereas the more active inhibitor of the deaminase, 2'-deoxycoformycin, does not. At 10 micron EHNA, which does not affect viability, growth, or DNA synthesis of uninfected HeLa cells, production of HSV and HSV-specific DNA is inhibited 75-90% and 60%, respectively. HSV multiplies normally in cells pretreated with EHNA and washed to remove this inhibitor. EHNA (10 micron) also markedly potentiates the toxicity of adenine arabinonucleoside and of cordycepin (3'-deoxyadenosine) against HeLa cells and against the production of HSV in those cells. Cordycepin alone (10 micron) does not inhibit HSV replication whereas in combination with 10 micron EHNA there is a greater than 99% inhibition of virus production. Under these conditions, RNA synthesis is inhibited by more than 80% whereas protein and DNA synthesis are inhibited to a lesser extent; in this system, virtually all of the DNA synthesis in infected cells is that of host DNA. Thus, EHNA appears to affect the synthesis of HSV DNA specifically in two different ways, depending on whether it is used alone or in the presence of cordycepin.

Adenine↗
PubMed1978

Polyamines of Anacystis nidulans and metabolism of exogenous spermidine and spermine.

Several biochemical parameters, including that of polyamine content, accompanying the growth of the cyanobacterium Anacystis nidulans were studied. At all stages of growth under autotrophic conditions, the organisms were found to be rich in spermidine and lacking in spermine, as is typical of procaryotic organisms. The cells were quite low in putrescine, and no unusual polyamine was observed to be present as a major component. Conjugated polyamines were not detected in the cultures. At maximal culture density, the levels of spermidine, DNA, RNA, protein, and chlorophyll were also maximal. Shortly after the inception of the stationary phase, the spermidine content of the cells was the first parameter observed to decrease in cultures which were shortly to become yellow. Spermidine lost from the cells was not recovered in the medium in a free or conjugated form. This indication of degradation of spermidine was studied by the addition of polyamines to growing cultures. Exogenous spermidine and spermine were found to be metabolized rapidly by the organisms, of which diaminopropane was one product. Putrescine was found to be markedly toxic, whereas spermidine, some other triamines, and spermine were much less toxic.

Chlorophyll↗
PubMed1977

The mechanisms of lethal action of arabinosyl cytosine (araC) and arabinosyl adenine (araA).

Certain D-arabinosyl nucleosides, notably arabinosyl cytosine (araC) and arabinosyl adenine (araA), are useful in the treatment of certain leukemias and some DNA virus infections, respectively. The compounds are lethal to animal cells and some bacteria. Despite extensive deamination, the parent nucleosides are transported within sensitive cells and phosphorylated to the mono-, di- and triphosphates. AraCTP and araATP are good specific competitive inhibitors of tumor cell of virus-induced DNA polymerases, competing with dCTP and dATP respectively. In addition to markedly inhibiting DNA synthesis, the aranucleotides enter newly formed DNA in internucleotide linkage. Sensitivity to the nucleosides appears to correlate with the relative ratio of formation of the triphosphate via a nucleoside kinase to degradation of the nucleoside via a nucleoside deaminase. Inhibition of the deaminase increases formation of the aranucleoside triphosphate in leukemic or virus-infected cells and markedly increases the toxicity of the nucleosides. Combinations of inhibitors of the deaminases and of the aranucleoside are being explored in clinical situations. In addition, the slow penetration of aranucleotides into cells has been observed and some of these 5'-phosphates are useful antiviral agents, e.g., against herpes virus in herpetic kiratitis.

Adenine↗