Part 1: synthesis of irreversible inhibitors of aldose reductase with subsequent development of a carbon-13 NMR protein probe. Part 2: synthesis of selenium analogs of dopamine as potential dopamine receptor agonists
Aldose reductase converts glucose into sorbitol using NADPH as a cofactor. Sorbitol accumulation in various tissues is believed to play a major role in the development of debilitating complications of diabetes; thus, much effort has been directed toward the preparation of aldose reductase inhibitors. Of the compounds prepared, the most active are the isothiocyanate and azide analogs of the reversible aldose reductase inhibitor alrestatin. The potency of the alrestatin isothiocyanate prompted the authors to examine the possibility that isothiocyanates enriched with carbon-13 could be used as carbon-13 NMR protein probes. Toward this end, a synthesis of carbon-13 enriched phenylisothiocyanate has been developed. This reagent has been successfully utilized to study peptides via carbon-13 NMR spectroscopy. Research in their laboratory over the years has focused on answering two fundamental questions regarding the interaction of dopamine with its receptor. First, can the concept of bioisosterism be applied to dopamine agonists. Secondly, what is the actual molecular species of dopamine which interacts with the dopamine receptor. In an effort to answer these questions, methyl selenide and dimethyl selenonium analogs of dopamine have been synthesized.
- Research Organization:
- Ohio State Univ., Columbus (USA)
- OSTI ID:
- 6479633
- Resource Relation:
- Other Information: Thesis (Ph. D)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CYANATES
SYNTHESIS
DOPAMINE
RECEPTORS
ENZYME INHIBITORS
CARBON 13
DIABETES MELLITUS
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
OXIDOREDUCTASES
REAGENTS
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARBON ISOTOPES
CARBONIC ACID DERIVATIVES
CARDIOTONICS
CARDIOVASCULAR AGENTS
DISEASES
DRUGS
ENDOCRINE DISEASES
ENZYMES
EVEN-ODD NUCLEI
HYDROXY COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MEMBRANE PROTEINS
METABOLIC DISEASES
NEUROREGULATORS
NITROGEN COMPOUNDS
NUCLEI
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
RESONANCE
SPECTRA
STABLE ISOTOPES
SYMPATHOMIMETICS
550200* - Biochemistry