Vitamin B12 conjugates with EPO, analogues thereof and pharmaceutical compositions

作者: Steven William Westwood , Gregory John Russell-Jones

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摘要: The invention describes complexes between VB12 analogues and either GCSF or EPO that retain both significant affinity for intrinsic factor (IF) in the portion of complex bioactivity complex. also concerns a process synthesis these complexes. This is achieved at least part, by using spacer compound, which linked covalantly EPO. preferably have formula V--X--A--Y--Z wherein V vitamin B12 analogue, derivative, bonded to X through carboxylate group pendant corrin nucleus central cobalt atom functional introduced onto molecule, selected from: --NHNH--, --NH--, --O--, --S--, --SS--or --CH2 --, A an optionally substituted, saturated unsaturated, branched linear, C1-50 alkylene, cycloalkylene aromatic group, with one more carbons within linear chain being replaced N, O S, optional substituents are from carbonyl, carboxy, hydroxy, amino other groups, Y covalent linkage Z where --NHCO--, --CONH--, --CONHNHCO--, --N═N--, --N═CH--, --NHCH2 --NHN═CH--, --NHNHCH2 --SS--, --SCH2 S--, --NHCRNH--, --COO--, --OCO--, R O, S NH2, reagents can be used as probes detection buried thiol groups protein peptide, said reagent comprising (or analogue thereof) generally any instrumentally visually detectable label, covalently diradical spacer, having terminal reactive capable forming disulphide bond free peptides.

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