SYNTHESIS OF 5'-SUBSTITUTED DERIVATIVES OF THE PYRROLO[2,3-D]-PYRIMIDINE NUCLEOSIDE SANGIVAMYCIN AND THEIR EFFECT ON PROTEIN KINASE-A AND KINASE-C ACTIVITY

被引:6
作者
SHARMA, M [1 ]
WIKIEL, H [1 ]
HROMCHAK, R [1 ]
BLOCH, A [1 ]
BOBEK, M [1 ]
机构
[1] ROSWELL PK CANC INST,DEPT EXPTL THERAPEUT,ELM & CARLTON ST,BUFFALO,NY 14263
来源
NUCLEOSIDES & NUCLEOTIDES | 1993年 / 12卷 / 3-4期
关键词
D O I
10.1080/07328319308017827
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Under cell-free conditions, where the antibiotic sangivamycin is not phosphorylated, it is an effective inhibitor of PKC and to a lesser extent of PKA activity. In intact cells, the antibiotic is phosphorylated, thereby, extending its range of activity to other targets including DNA and RNA. To preserve selective inhibitory activity for the protein kinases, analogs potentially resistant to phosphorylation were prepared by replacing the 5'-hydroxy group with O-nitro, O-sulfamoyl, O-methane-sulfonyl or azido groups. These compounds were more potent inhibitors of PKA and PKC activity than was the parent nucleoside.
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页码:295 / 304
页数:10
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