PubMed Health⌕ Search

Biomedical subjects

S Benkovic

Publications and source records attributed to S Benkovic.

4 recordsLinked to original sources
PubMed1994

Effect of a thiobenzimidazolone derivative on DNA strand transfer catalyzed by HIV-1 reverse transcriptase.

Thiobenzimidazolone (TIBO) derivatives are known inhibitors of the DNA polymerase activity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). The effect of a TIBO derivative ((+)-S-4,5,6,7-tetrahydro-9-chloro-5- methyl-6-(3-methyl-2-butenyl)-imidazol[4,5,1-jk]1,4-benzodiazapine -2-thione ) on the DNA strand transfer reaction catalyzed by HIV-1 RT (which is a function of both the DNA polymerase and RNase H activities) was investigated by delineating the effect of the drug on the constitutive DNA polymerase and RNase H activities) was investigated by delineating the effect of the drug on the constitutive DNA polymerase and RNase H activities. Single nucleotide incorporation on template-primer 1 was used to study the DNA polymerase activity of HIV-1 RT while template-primer 2 was used to study the effect of TIBO on the RNase H activity (polymerase independent). The drug was found to decrease the amplitude of the presteady-state burst when preequilibrated with the enzyme-substrate complex besides decreasing the steady-state rate of single nucleotide incorporations. In the absence of preincubation, TIBO did not affect the burst amplitude but decreased the steady-state rate after the pre-transient phase. This suggested that binding of TIBO to RT was affected by the presence of template-primer and required dissociation of the enzyme from the template-primer for effective binding. The polymerase-independent RNase H activity was activated in the presence of TIBO. The effect of TIBO on the overall process of DNA strand transfer is a balance between its inhibition of the polymerase activity and its activation of the RNase H activity.

Antiviral Agents↗
PubMed1994

Catalytic antibodies: perusing combinatorial libraries.

Combinatorial libraries are a promising alternative for isolating catalytic antibodies produced by the immune system in response to the transition-state analog of a given reaction. Large, diverse panels of antibodies with high affinity for the transition-state analog can be isolated using screening or selection approaches. Furthermore, we have estimated that nucleotide sequences that bear close similarity to the sequence for a known catalytic antibody occur in combination at frequencies sufficient for their detection in such libraries.

Amino Acid Sequence↗
PubMed1991

Localization of insulin-like growth factor-1 mRNA in murine central nervous system during postnatal development.

Insulin-like growth factor-1 (IGF-1) is believed to play a role in the regulation of brain growth. The identity of cells responsible for its synthesis in the immature brain, however, has not been established. To identify potential sites of IGF-1 synthesis, in situ hybridization has been utilized to localize IGF-1 mRNA in the murine brain during the first postnatal month. Although IGF-1 mRNA was detected in all regions of the neonatal brain, there was considerable regional variation in the level of expression. Neurons were the principle sites IGF-1 mRNA expression and expression was typically restricted to one or two neuronal cell types within each region. In the cerebellar cortex, for example, only Purkinje cells hybridized to the IGF-1 probe. In contrast to gray matter, IGF-1 labeled cells were rarely found in presumptive white matter tracts of the forebrain. The hybridization signal was most prominent in regions where neurogenesis persisted after birth, including the cerebellum, olfactory bulb, and hippocampal complex. The timing of IGF-1 mRNA expression appeared to be temporally related to local neuronal proliferation. The number of labeled cells and intensity of hybridization signal was greatest during the first 2 postnatal weeks, a period of rapid neuronal proliferation in these regions. At the end of the first month, when neurogenesis had essentially ceased, IGF-1 signal strength had declined to background levels. The temporal and spatial pattern IGF-1 mRNA expression in the immature CNS was consistent with a role for locally produced IGF-1 in the regulation of brain development.

Aging↗