| 主权项 |
1. A method for linking a compound of formula R1—H which comprises a first functional moiety of formula F1 to a second functional moiety of formula F2 with a reagent which is a compound of formula (Ia) wherein:
X and X′ each represent oxygen;Y is an electrophilic leaving group;either:
R3 and R3′ together form a group of formula —N(R33′), wherein R33′ represents a hydrogen atom or a group of formula Y, Nu, -L(Z)n or IG; orR3 and R3′ together form a group of formula —N(R33′)—N(R33′)— wherein each R33′ is the same or different and represents a hydrogen atom or a group of formula Y, Nu, -L(Z)n or IG;R2 represents a hydrogen atom or a group of formula Y, Nu, -L(Z)n or IG;each group of formula Y is the same or different and represents an electrophilic leaving group;each group of formula Nu is the same or different and represents a nucleophile selected from —OH, —SH, —NH2, and —NH(C1-6 alkyl);each group of formula L is the same or different and represents a linker group;each group of formula Z is the same or different and represents a reactive group attached to a group of formula L which his capable of reacting with a compound containing a second functional moiety such that said second function moiety becomes linked to said group of formula L;n is 1, 3, or 3; andeach group of formula IG is the same of different and represents a moiety which is a C1-20 alkyl group, a C2-20 alkenyl group or a C2-20 alkynyl group, which is unsubstituted or substituted by one or more substituents selected from halogen atoms and sulfonic acid groups, and in which (a) 0, 1, or 2 carbons atoms are replaced by groups selected from C6-10 arylene, 5- to 10-membered heterocyclylene groups, and (b) 0, 1 or 2 —CH2— groups are replaced by groups selected from —O—, —S—, —S—S—, —C(O)— and —N(C1-6 alkyl); groups, wherein;
(i) said arylene, heteroarylene, carbocyclylene and heterocyclene groups are unsubstituted or substituted by one or more substituents selected from halogen atoms, and C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthiol, —N(C1-6 alkyl)(C1-6 alkyl), nitro, and sulfonic acid groups; and(ii) 0, 1, or 2 carbons atoms in said carbocyclylene and heterocyclylene groups are replaced by —C(O)— groups; the first functional moiety and the second functional moiety are the same or different and are each selected from a detectable moiety, an enzymatically active moiety, an affinity tag, a hapten, an immunogenic carrier, an antibody or antibody fragment, an antigen, a ligand, a biologically active moiety, a liposome, a polymeric moiety, an amino acid, a peptide, a protein, a carbohydrate, a DNA and an RNA;wherein method comprises attaching the group R1 to the compound of formula (Ia) via nucleophilic attack of the first δH group in the compound of formula R1—H at the 2-position of the compound of formula (Ia), such that the group Y at the 2-position is replaced by the group R1. |
