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Purine Metabolism Enzymes
Purine and pyrimidine nucleotides are universal metabolites of all earth-living organisms. Buiding blocks of DNA, RNA and coenzymes, they are also key players of numerous cell metabolism processes: energy vehicles, precursors of lipids and sugars biosynthesis, source of methylation, mediators of cell signalling and neurotransmission. Nucleosides and nucleotides metabolism, and therefore purine metabolism enzymes are therefore an important area of research in cell biology and in health science.
For the Drug Discovery industry, purine metabolism represents a rich source of validated or high-potential targets in Oncology, Infectiology and Immunology. The impact of drugs on nucleotides metabolism is a major concern for these therapeutic fields. NOVOCIB produces recombinant purine metabolism enzymes, among which are such validated targets against cancer, infectious diseases or immunological disorders.
Purine and pyrimidine nucleotides are universal metabolites of all earth-living organisms. Buiding blocks of DNA, RNA and coenzymes, they are also key players of numerous cell metabolism processes: energy vehicles, precursors of lipids and sugars biosynthesis, source of methylation, mediators of cell signalling and neurotransmission. Nucleosides and nucleotides metabolism, and therefore purine metabolism enzymes are therefore an important area of research in cell biology and in health science.
For the Drug Discovery industry, purine metabolism represents a rich source of validated or high-potential targets in Oncology, Infectiology and Immunology. The impact of drugs on nucleotides metabolism is a major concern for these therapeutic fields. NOVOCIB produces recombinant purine metabolism enzymes, among which are such validated targets against cancer, infectious diseases or immunological disorders.
IMPDH - Inosine Monophosphate Dehydrogenase (E.C.1.1.1.205)
Synonyms: inosine 5'-monophosphate dehydrogenase, type 2, IMP dehydrogenase, type II, IMPDH2
Inosine Monophosphate Dehydrogenase (IMPDH) converts inosine 5’-monophosphate (IMP) to xanthosine 5’- monophosphate (XMP) using NAD+ as a cofactor. This step is crucial for guanosine biosynthesis and to feed the pool of guanine nucleotides. IMPDH is a validated target for several therapeutic applications (cancer, immunological disorders...). Several IMPDH inhibitors, including blockbusters (e.g. CellCept®), have shown their clinical efficacy. Besides nucleoside (or NAD) analogues, new chemical entities (NCEs) have been identified as efficient IMPDH inhibitors and are currently investigated.
Recombinant Bacterial IMPDH from Staphylococcus aureus is also available either to assess the specificity of Human IMPDH inhibitors or to screen compounds that inhibit bacterial IMPDH, which is a recognized target for the development of new antibiotics.
Recombinant Bacterial IMPDH from Staphylococcus aureus is also available either to assess the specificity of Human IMPDH inhibitors or to screen compounds that inhibit bacterial IMPDH, which is a recognized target for the development of new antibiotics.
To know more about NovoCIB's IMPDH enzymes
To evaluate Nucleoside Analogues as potential IMPDH inhibitors, see also our
Nucleoside Kinase - IMPDH coupled assay
Nucleoside Kinase - IMPDH coupled assay
PNP - Purine Nucleoside Phosphorylase (E.C.2.4.2.1) (^Top)
Purine Nucleoside Phosphorylase (PNP) catalyzes the cleavage of the glycosidic bond of ribo- or deoxyribonucleosides to generate purine base and ribose- or deoxyribose-1-phosphate. The reaction is reversible for natural substrates.
A target: PNP inhibitors are investigated for chemotherapeutic applications in T-cell leukemia and T-cell-mediated autoimmune disorders, such as SLE and RA. Several PNP inhibitors have been developed to treat cancer, viral infection and auto-immune diseases.
A drug-deactivating enzyme: PNP's cleaving activity can also be responsible for the deactivation of Nucleoside Analogues. Their resistance to human PNP can be investigated in vitro to better evaluate the efficacy of the drugs.
Besides its two pharmacological properties, PNP can also be a powerful tool for drug chemistry of nucleoside analogues. Due to its reversible cleaving activity, PNP can help to considerably increase the yield of transribosylation reactions and circumvent synthesis difficulties.
A target: PNP inhibitors are investigated for chemotherapeutic applications in T-cell leukemia and T-cell-mediated autoimmune disorders, such as SLE and RA. Several PNP inhibitors have been developed to treat cancer, viral infection and auto-immune diseases.
A drug-deactivating enzyme: PNP's cleaving activity can also be responsible for the deactivation of Nucleoside Analogues. Their resistance to human PNP can be investigated in vitro to better evaluate the efficacy of the drugs.
Besides its two pharmacological properties, PNP can also be a powerful tool for drug chemistry of nucleoside analogues. Due to its reversible cleaving activity, PNP can help to considerably increase the yield of transribosylation reactions and circumvent synthesis difficulties.
To know more about NovoCIB's PNP enzyme
HGPRT - Hypoxanthine-guanine phosphoribosyltransferase (E.C.2.4.2.8) (^Top)
Synonyms: hypoxanthine phosphoribosyltransferase (HPRT)
NOVOCIB's human HGPRT is a recombinant protein of ca. 25kDa cloned by RT-PCR amplification of mRNA extracted from human hepatoma cells and expressed in E.coli. The sequence of the cloned HGPRT (accession number P00492) was confirmed by DNA sequencing (100% identity).
Hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) is a purine salvage enzyme that catalyzes the reversible transfer of the 5-phosphoribosyl group between α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) and a purine base (hypoxanthine or guanine) to form a purine nucleotide IMP or GMP. The reaction is reversible but forward reaction (nucleotide formation) is heavily favoured.
Hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) is a purine salvage enzyme that catalyzes the reversible transfer of the 5-phosphoribosyl group between α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) and a purine base (hypoxanthine or guanine) to form a purine nucleotide IMP or GMP. The reaction is reversible but forward reaction (nucleotide formation) is heavily favoured.
To know more about NovoCIB's HGPRT enzyme
| Related Links | |
| • IMPDH enzyme
• PNP enzyme • HGPRT enzyme • Nucleoside Kinases |
• IMPDH Inhibition Screening
• PNP Inhibition Screening • AK Inhibition • dCK Inhibition |
Other enzymes and related services are continuously under development at NOVOCIB. Please, do not hesitate to visit us regularly or to contact us.