> compound that block DNA replication in human cell

[lorenzo.costantino]

hi all,

i'm looking for a compound that is able to block DNA replication in human cell, can be a nucleotide analogue or some other compound. the best one it would be a compound that is incorporated into the DNA during replication and after incorporation the replication fork is not able to go on anymore or the remove the compound..

someone can help me out???

thank you

[Winter]

Probably, the molecules that best fit your definition are the dideoxynucleotides (ddNTPs), the chain terminators used for the Sanger's DNA sequencing method.

[lorenzo.costantino]

but are you sure that ddNTPs are stably incorporated in vivo?? i thought that the proof reading action of the polymerase is able to eliminate the ddNTPs from the newly synthesized DNA???
pls help me

[Winter]

Then, maybe dinucleoside tetraphosphates is what you are looking for.

"We have synthesized and purified several dinucleoside tetraphosphates (ddAp4ddA, ddCp4ddC, ddGp4ddG, ddTp4ddT, Ap4ddG, 2′(3′)-O-(N-methylanthraniloyl)-Ap4ddG, and AppNHppddG) and show that these compounds can serve as substrates for DNA chain elongation and termination resulting in inhibition of DNA synthesis"

From the abstract of Meyer et al. 2006.

[lorenzo.costantino]

the problem here the use of tetraphosphate nucleotides how cannot pass easily the membrane and enter the cell. in this paper they try to inhibit the HIV DNA transcription but not the cell DNA one.
any other suggestion is welcome!!!

[lorenzo.costantino]

but i think that using a tetra phosphate will be a problem to enter the cell membrane. and in the paper they block the DNA synthesis of HIV but they don't mention on the effect on the DNA replication in the cell.
any other suggestions???
thanks a lot

Originally Posted by Winter

Then, maybe dinucleoside tetraphosphates is what you are looking for.

"We have synthesized and purified several dinucleoside tetraphosphates (ddAp4ddA, ddCp4ddC, ddGp4ddG, ddTp4ddT, Ap4ddG, 2′(3′)-O-(N-methylanthraniloyl)-Ap4ddG, and AppNHppddG) and show that these compounds can serve as substrates for DNA chain elongation and termination resulting in inhibition of DNA synthesis"

From the abstract of Meyer et al. 2006.

[lorenzo.costantino]

i think that using a tetra phosphate will be a problem for passing the cell membrane of the cell. and also they use this compounds to inhibit the HIV DNA replication but they don't mention about DNA replication of the cell.

any other suggestion??