METHOD FOR CONTROLLING THE FIDELITY AND EXECUTION OF REVERSE TRANSCRIPTASE BY INCORPORATING AND POLYMERISING NUCLEOTIDE ANALOGUES ACCEPTABLE AS SUBSTRATES WITHOUT BLOCKING ITS ELONGATION

摘要

The invention concerns the use of nucleotide analogues, defined as molecules acceptable as substrate of the reverse-transcription response and enabling the addition of at least one supplementary nucleotide to the polynucleotide chain during the reverse transcription to affect and/or to control the fidelity and execution of the reverse transcription. The invention also concerns a pharmaceutical composition containing said nucleotide analogues preferably selected among dUTP, dITP, C7dGTP and C7dATP or characterised in that they have modified bases 6H, 8H-3,4-dihydropyrimido[4,5c][1,2]oxazin-7-one (P) and N methoxy-2,6-diaminopurine (K) alone or mixed with 3'-azido-3'deoxythimidine(AZT), 2',3'-dideoxyinosine-(ddI), 2',3'-dideoxycytidine (ddC), (-)2',3'-dideoxy-3'-theacytidine (3TC), 2',3'-didehydro-2',3'-dideoxythymidine (d4T) and (-)2'-deoxy-5-fluoro-3'-theacytidine (FTC), TIBO (tetrahydroimidazo-(4,5,1-1,jk) (1,4)-benzodiapezine-2-(1H)-one, HEPT (1-[(2-hydroxyethoxy)-methyl]-6-phenylthiothymine), TSAO([2', 5'-bis-O-(tert-butylmethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-dioxide), α-APA (alpha-anilinophenylacetamide), neviparine, BAHP (bis(etheroaryl)-piperazine) or phosphonoformic acid (PFA), indinavir, saquinavir.