New lanthanide chelate compounds useful for marking bioactive substance e.g. oligopeptide, oligonucleotide, polynucleotide, oligosaccharide, polysaccharide, phospholipid or peptide nucleic acid, either in solution or on solid phase

摘要

Lanthanide chelate compounds (I) for marking bioactive substance in solution, are new. Lanthanide chelate compounds of formula (I) for marking bioactive substance in solution, are new. A : reactive group for binding biomolecule, comprising isothiocyanate, bromoacetamido, iodoacetamido, maleimide, 4,6-dichloro-1,3,5-triazinyl-2-amino, pyridyldithiol, thioester, aminooxy, azide, alkyne, hydrazide, amino, carboxylic acid, ester or acid halide; Z 1-Z 3H or an electron donating group; Z 4an electron donating group; Z 5a substituent containing carboxylic acid group, phosphoric acid group or sulfonic acid group; X : linker formed from 1-10 groups of 3-12C alkyl or T; T : phenyl, ethyne-diyl, ethene-diyl, ether, thioether, amide (-CO-NH-, -CO-NR1aa-, -NH-CO- or -NR1aa-CO-), carbonyl, ester, disulfide, sulfonamide (-SO 2-NH-, -NH-SO 2-, -NR1aa-SO 2- or -SO 2-NR1aa-), sulfonyl, phosphate, diaza or tert-amine (-NR1aa-); R1aa : alkyl having less than five C; R1a, R1b, R1c, R1d : carboxylic acid or its salt, or an amide (-CO-NH 2or -CO-NHR1aa); and Ln : terbium, dysprosium, samarium or europium. An independent claim is included for a marking reagent comprising a substituted pyridine compound of formula (II) for marking bioactive substance on the surface of a hard phase. R : -COOR1b or -CONHR1b; R1b : phenyl or benzyl (both optionally substituted) or 1-4C alkyl; Z 5a substituent containing carboxylic acid ester, sulfonic acid or sulfonic acid ester; X : 1-2C alkyl or T; A : reactive group for binding to biomolecule, comprising carboxylic acid or its salt, acid halide, ester or amino acid group of formula (-CH(NHR 2)R 3), or -E-O-PZ-O-R 4, where O is substituted selectively by S; R 2temporary protecting group; Z : Cl or NR 5R 6; R 4protecting group; R 5, R 6alkyl; and E : absent or radical of purine or pyrimidine base, which is bond to O either by the hydrocarbon chain, which is substituted with a protected hydroxyethyl group, or by a furan or pyran ring or their modified derivatives, which enables oligonucleotide synthesis. [Image] [Image].