Biomaterial Database

Enzymatically activated cycloSal-d4T-monophosphates: The third generation of cycloSal-pronucleotides. 2007

Nicolas Gisch, and Jan Balzarini, and Chris Meier

Department of Chemistry, Organic Chemistry, Faculty of Sciences, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany.

The third generation of cycloSal-pronucleotides, 5-diacetoxymethyl-cycloSal-d4T-monophosphates (5-di-AM-cycloSal-d4TMPs), is reported as a new class of "lock-in"-modified cycloSal-pronucleotides. These compounds bear an esterase-cleavable geminal dicarboxylate (acylal) attached to the aromatic ring of the saligenyl unit. The conversion into a strong acceptor group (aldehyde) leads to a strong decrease in hydrolytic stability. As a consequence, a fast release of a nucleoside monophosphate (i.e., d4TMP) follows. The concept of this enzymatic activation is proven by hydrolysis studies in phosphate buffer, cell extracts, and human serum. These investigations showed the conversion of the acylal group into a polar aldehyde by enzymatic cleavage. Besides, antiviral activities against HIV are presented.

UI	MeSH Term	Description	Entries
D010755	Organophosphates	Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(	Organophosphate,Phosphates, Organic,Phosphoric Acid Esters,Organopyrophosphates,Acid Esters, Phosphoric,Esters, Phosphoric Acid,Organic Phosphates
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006868	Hydrolysis	The process of cleaving a chemical compound by the addition of a molecule of water.
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013936	Thymidine	A nucleoside in which THYMINE is linked to DEOXYRIBOSE.	2'-Deoxythymidine,Deoxythymidine,2' Deoxythymidine
D013942	Thymine Nucleotides	Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154)	Thymidine Phosphates,Nucleotides, Thymine,Phosphates, Thymidine
D054306	Dideoxynucleotides	The phosphate esters of DIDEOXYNUCLEOSIDES.	Dideoxynucleotide Triphosphates,ddNTPs,Triphosphates, Dideoxynucleotide
D018119	Stavudine	A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.	2',3'-Didehydro-3'-deoxythymidine,D4T,2',3'-Didehydro-2',3'-dideoxythmidine,BMY-27857,Stavudine, Monosodium Salt,Zerit,2',3' Didehydro 3' deoxythymidine,BMY 27857,BMY27857
D019380	Anti-HIV Agents	Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.	AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV