Modified nucleotides for synthesis of nucleic acids, a kit containing such nucleotides and their use for the production of synthetic nucleic acid sequences or genes

A modified nucleotide comprising:

• a “natural” nitrogenous base or a natural nitrogenous base analog, a ribose or deoxyribose carbohydrate, and at least one phosphate group,
• at least one R or R′ group, called modifier group, borne:
• by said natural nitrogenous base or analog,
• and/or by the oxygen in position 3′ of the ribose or deoxyribose molecule, making it possible to block the polymerization of said nucleotide and/or to allow the interaction of said nucleotide with another molecule, different than another nucleotide, such as a protein, during nucleic acid synthesis, R comprising at least one functional end group, said nucleotide being in the form of one of formulae (I), (III) and (IV) below:
• in which:
• (PP)PO represents a mono-, di- or triphosphate group,
• (OH) describes the possibility of a ribose or deoxyribose molecule,
• T is a hydrogen, or a cleavable radical chosen from —NH2, —N3, —(C═O)H, —CnH2n+1 with n between 1 and 30, preferably between 1 and 12, -trimethylsilyl, -phosphate, —SO3, —(C═O)OCnH2n+1 with n between 1 and 30, preferably between 1 and 12, —(C═O)SCnH2n+1 with n between 1 and 30, preferably between 1 and 12, -nitrobenzene, -benzyl, -halobenzyl, -amide, -carbonate, -benzoyl, -peroxyl, -nitrile, -thiol, -imide, -carbamate, -cyanate, -alkyne, -phenyl, -halophenyl, -picolyl,
• M, which is optionally present, is a group covalently bonded to Q and to Z, M being chosen from alkyl, alkenyl, alkyne, aryl, alkylaryl, heteroaryl, acyl, alkyloxy, alkylamino, alkoxyamino, amido, alkylimido, alkenylimido, arylimido, fluoroalkyl, alkylphosphate, alkylthio, thioacyl, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, alkylammonium, alkylsulfonium, alkylsilyl, alkylcarbonyl, alkylcarbanyl, alkylcarbamoyl or alkylhydroxylamino,
• Z is a cleavable -nitrophenyl-group,
• Q is an end functional, or effector, group of the R or R′ group, Q being chosen from biotin, a protein, a polynucleotide of defined sequence, a carbohydrate, an antigen, a hormone, a neurotransmitter, a glycoside such as digoxin, a sulfur-containing radical, in particular bearing a thiol function, such as glutathione, or a bidentate ligand such as catechol,
• R and R′ possibly being present independently or simultaneously, and when R and R′ are present simultaneously:
• the Z groups may be identical or different,
• the M groups may be identical or different,
• the Q groups may be identical or different,
• “base” represents a “natural” nitrogenous base chosen from adenine, thymine, cytosine, guanine or uracil or a natural nitrogenous base analog, with the exception of thymine when R′ is present and Q comprises biotin.