Application of the cycloSal-prodrug approach for improving the biological potential of phosphorylated biomolecules

被引:58
作者
Meier, C.
Balzarini, J.
机构
[1] Univ Hamburg, Inst Organ Chem, D-20146 Hamburg, Germany
[2] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium
关键词
nucleoside analogs; antiviral agent; cycloSal-pronucleotides; carbohydrate drugs;
D O I
10.1016/j.antiviral.2006.04.011
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Pronucleotides represent a promising tool to improve the biological activity of nucleoside analogs in antiviral and cancer chemotherapy. The cycloSal-approach is one of several conceptually different pronucleotide systems. This approach can be applied to various nucleoside analogs. A salicyl alcohol as a cyclic bifunctional masking unit is used, and shown to afford a chemically driven release of the particular nucleotide from the lipophilic phosphate triester precursor molecule. A conceptual extension of the cycloSal-approach results in the design of "lock-in"-cycloSal-derivatives. The cycloSal-approach is not restricted to the delivery of bioactive nucleotides but also useful for the intracellular delivery of hexose-1-phosphates. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:282 / 292
页数:11
相关论文
共 38 条
[11]  
Ducho Christian, 2002, Antivir Chem Chemother, V13, P129
[12]   Effects of cycloSal-d4TMP derivatives in H9 cells with induced AZT resistance phenotype [J].
Gröschel, B ;
Meier, C ;
Zehner, R ;
Cinatl, J ;
Doerr, HW ;
Cinatl, J .
NUCLEOSIDES & NUCLEOTIDES, 1999, 18 (4-5) :933-936
[13]   FAMILIAL PSYCHOMOTOR RETARDATION WITH MARKEDLY FLUCTUATING SERUM PROLACTIN, FSH AND GH LEVELS, PARTIAL TBG-DEFICIENCY, INCREASED SERUM ARYLSULFATASE-A AND INCREASED CSF PROTEIN - NEW SYNDROME [J].
JAEKEN, J ;
VANDERSCHUERENLODEWEYCKX, M ;
CASAER, P ;
SNOECK, L ;
CORBEEL, L ;
EGGERMONT, E ;
EECKELS, R .
PEDIATRIC RESEARCH, 1980, 14 (02) :179-179
[14]   Synthesis and properties of fluorescent cycloSal nucleotides based on the pyrimidine nucleoside m5K and its 2′,3′-dideoxy analog dM5K [J].
Jessen, HJ ;
Fendrich, W ;
Meier, C .
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2006, 2006 (04) :924-931
[15]   Evidence for cyclophosphate formation during hydrolysis of 3-methyl-cycloSal-PCVMP [J].
Lomp, A ;
Meier, C ;
Herderich, M ;
Wutzler, P .
NUCLEOSIDES & NUCLEOTIDES, 1999, 18 (4-5) :943-944
[16]   Cyclo-saligenyl-5-fluoro-2'-deoxyuridinemonophosphate (cycloSal-FdUMP) - A new prodrug approach for FdUMP [J].
Lorey, M ;
Meier, C ;
DeClercq, E ;
Balzarini, J .
NUCLEOSIDES & NUCLEOTIDES, 1997, 16 (7-9) :1307-1310
[17]   Cytosolic and mitochondrial deoxyribonucleotidases: activity with substrate analogs, inhibitors and implications for therapy [J].
Mazzon, C ;
Rampazzo, C ;
Scaini, MC ;
Gallinaro, L ;
Karlsson, A ;
Meier, C ;
Balzarini, J ;
Reichard, P ;
Bianchi, V .
BIOCHEMICAL PHARMACOLOGY, 2003, 66 (03) :471-479
[18]   Inhibitory effect of cycloSaligenyl-nucleoside monophosphates (cycloSal-NMP) of acyclic nucleoside analogues on HSV-1 and EBV [J].
Meerbach, A ;
Klöcking, R ;
Meier, C ;
Lomp, A ;
Helbig, B ;
Wutzler, P .
ANTIVIRAL RESEARCH, 2000, 45 (01) :69-77
[19]   cycloSal-pronucleotides of 2′,3′-dideoxyadenosine and 2′,3′-dideoxy-2′,3′-didehydroadenosine:: Synthesis and antiviral evaluation of a highly efficient nucleotide delivery system [J].
Meier, C ;
Knispel, T ;
De Clercq, E ;
Balzarini, J .
JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (09) :1604-1614
[20]   Second-generation cycloSal-d4TMP pronucleotides bearing esterase-cleavable sites -: the "trapping" concept [J].
Meier, C ;
Ducho, C ;
Jessen, H ;
Vukadinovic-Tenter, D ;
Balzarini, J .
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2006, 2006 (01) :197-206