Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:108-67-8 (TMB)
 1,625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The synthesis of alpha-D-glucopyranosyl 1-(methylenediphosphonate) (11), alpha-D-galactopyranosyl 1-(methylenediphosphonate) (14), and alpha-D-mannopyranosyl 1-(methylenediphosphonate) (17) has been accomplished. [(Di-phenoxyphosphinyl)methyl]phosphonic acid (diphenyl-MDP) (5), synthesized by two different procedures, was fused with beta-D-glucopyranose pentaacetate followed by catalytic hydrogenation to give 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl methylenediphosphonate (glucose-MDP) (10). The anomeric configuration of 10 was assigned on the basis of NMR spectral studies. Condensation of 10 with 2',3'-di-O-acetyladenosine was accomplished by using 1-(mesitylene-2-sulfonyl)-3-nitro-1,2,4-triazole (MSNT) as coupling agent, and removal of the blocking groups gave adenosine 5'-[(alpha-D-glucopyranosylhydroxyphosphinyl)methyl]phosphonate (20). Uridine 5'-[(alpha-D-galactopyranosylhydroxyphosphinyl)methyl] phosphonate (23) and guanosine 5'-[(alpha-D-mannopyranosylhydroxyphosphinyl)methyl]phosphonate (26) were similarly prepared. Using a specific glycoprotein galactosyltransferase (EC 2.4.1.38) assay, uridine 5'-[(alpha-D-galactopyranosylhydroxyphosphinyl)methyl]phosphonate (23) demonstrated competitive inhibition with an apparent Ki of 97 microM. The adenosine analogue did not inhibit the enzyme. None of the above compounds show any in vitro antitumor or antiviral activity. Such specific inhibitors of glycosyltransferases may serve as specific probes to study various glycosyltransferases that might be involved in the process of metastasis.
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PMID:Synthesis of certain nucleoside methylenediphosphonate sugars as potential inhibitors of glycosyltransferases. 347 72

Potential prodrugs of the highly insoluble, diimide antitumor agent mitindomide (1b) were synthesized by several different methods. The condensation reaction between mitindomide and formaldehyde cleanly gave the stable bis(hydroxymethyl) compound 7a, which was partially soluble in water (ca. 0.8%) and showed improved activity in the P-388 screen. When this compound was treated with secondary amines, good yields of Mannich bases could be isolated. The compound from N-methylpiperazine (7b) had excellent properties and is a candidate for clinical trials. Condensation with other aldehydes gave either no reaction or compounds with poor activity. A water-soluble ester was prepared from 7a and succinic anhydride, but had reduced potency and activity. Oxidation of the double bond of 1a with ozone gave an inactive diacid, whereas the dihydro compound was as active as the olefin. When other aromatics (anisole, p-xylene, mesitylene) were photolyzed with maleimide, the resulting photoproducts were found to be inactive. Diimides from other ring system were synthesized from the corresponding anhydrides and found to be inactive. However, the bis(hydroxymethyl) derivative of one of these (12a) was active in the P-388 screen.
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PMID:Synthesis of congeners and prodrugs of the benzene maleimide photoadduct mitindomide as potential antitumor agents. 2. 378 77

Herein we report the synthesis of tripodal C3-symmetric opioid scaffolds as high-affinity condensation agents of duplex DNA. Condensation was achieved on both supercoiled and canonical B-DNA structures and identified by agarose electrophoresis, viscosity, turbidity and atomic force microscopy (AFM) measurements. Structurally, the requirement of a tris-opioid scaffold for condensation is demonstrated as both di- (C2-symmetric) and mono-substituted (C1-symmetric) mesitylene-linked opioid derivatives poorly coordinate dsDNA. Condensation, observed by toroidal and globule AFM aggregation, arises from surface-binding ionic interactions between protonated, cationic, tertiary amine groups on the opioid skeleton and the phosphate nucleic acid backbone. Indeed, by converting the 6-hydroxyl group of C3-morphine ( MC3: ) to methoxy substituents in C3-heterocodeine ( HC3: ) and C3-oripavine ( OC3: ) molecules, dsDNA compaction is retained thus negating the possibility of phosphate-hydroxyl surface-binding. Tripodal opioid condensation was identified as pH dependent and strongly influenced by ionic strength with further evidence of cationic amine-phosphate backbone coordination arising from thermal melting analysis and circular dichroism spectroscopy, with compaction also witnessed on synthetic dsDNA co-polymers poly[d(A-T)2] and poly[d(G-C)2]. On-chip microfluidic analysis of DNA condensed by C3-agents provided concentration-dependent protection (inhibition) to site-selective excision by type II restriction enzymes: BamHI, HindIII, SalI and EcoRI, but not to the endonuclease DNase I.
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PMID:C 3-symmetric opioid scaffolds are pH-responsive DNA condensation agents. 2789 72