Conjugated proteins and peptides

1. A compound of the general formula:

in which X represents a polymer;

Q represents a linking group;

W represents an electron-withdrawing moiety or a moiety preparable by reduction of an electron-withdrawing moiety;

each of R 1 and R 2 independently represents a hydrogen atom or a C 1-4 alkyl group; and

either Z 1 represents a protein or a peptide linked to CR 2 via a nucleophilic moiety, and

Z 2 represents a molecule linked to CR 2 via a nucleophilic moiety, or Z 1 and

Z 2 together represent a single group derived from a protein or peptide linked to CR 2 via two nucleophilic moieties.

2. A compound as claimed in claim 1 , in which X is a polyalkylene glycol, a polyvinylpyrrolidone, a polyacrylate, a polymethacrylate, a polyoxazoline, a polyvinylalcohol, a polyacrylamide or polymethacrylamide, a HPMA copolymer, a polyester, polyacetal, poly(ortho ester), polycarbonate, poly(imino carbonate), a polyamide, a copolymer derived from two or more alkylene oxides or from an alkylene oxide and a polyester, polyacetal, poly(ortho ester), or a poly(amino acid), a copolymer of divinylether-maleic anhydride and styrene-maleic anhydride, a polysaccharide, polyglutamic acid, or a copolymer of a saccharides or an amino acid with an alkylene oxide or methacrylic acid.

3. A compound as claimed in claim 1 , in which X is a water-soluble synthetic polymer.

4. A compound as claimed in claim 3 , in which X is a polyethylene glycol.

5. A compound as claimed in claim 1 , in which Q is a direct bond, an alkylene group, or an optionally-substituted aryl or heteroaryl group, any of which may be terminated or interrupted by one or more oxygen atoms, sulphur atoms, —NR groups in which R represents a hydrogen atom or an alkyl or aryl group, keto groups, —O—CO— groups and/or —CO—O— groups.

6. A compound as claimed in claim 5 , in which W represents a keto group CO, an ester group —O—CO—, an amide group —NH—CO—, or a sulphone group —SO 2 —, or a group obtained by reduction of such a group.

7. A compound as claimed in claim 1 , in which Z 1 and Z 2 together represent a single group derived from a protein.

8. A compound as claimed in claim 7 , in which Z 1 and Z 2 together form a single group derived from a protein which is linked to CR 2 via two thiol groups which have been derived from a disulfide bridge in the protein.

9. A compound as claimed in claim 7 , in which Z 1 and Z 2 together form a single group derived from a protein which is linked to CR 2 via two histidine residues.

10. A compound as claimed in claim 9 , in which said two histidine residues form part of a polyhistidine tag.

11. A compound of the general formula II:

X-Q-W′—CR 1 R 1 ′—CR 2 .L.L′  (II)

in which X represents a polymer;

Q represents a direct bond, an alkylene group, or an optionally-substituted aryl or heteroaryl group, any of which may be terminated or interrupted by one or more oxygen atoms, sulphur atoms, —NR— groups in which R represents a hydrogen atom or an alkyl or an aryl group, keto groups, —O—CO— groups and/or —CO—O— groups;

W′ represents an electron-withdrawing group;

either R 1 represents a hydrogen atom or a C 1-4 alkyl group, R 1′ represents a hydrogen atom, and each of L and L′ independently represents a leaving group; or

R 1 represents a hydrogen atom or a C 1-4 alkyl group, L represents a leaving group, and R 1 ′ and L′ together represent a bond; or

R 1 and L together represent a bond and R 1 ′ and L′ together represent a bond; and

R 2 represents a hydrogen atom or a C 1-4 alkyl group;

provided that when Q represents a direct bond, R 1 represents a hydrogen atom or a C 1-4 alkyl group.

12. A compound as claimed in claim 11 , in which a leaving group L or L′ represents —SR, —SO 2 R, —OSO 2 R, —N + R 3 , —N + HR 2 , —N + H 2 R, halogen, or —OØ, in which R represents a hydrogen atom or an alkyl or an aryl group, and Ø represents a substituted aryl group containing at least one electron-withdrawing substituent.

13. A compound as claimed in claim 11 , in which W′ represents a keto group, an ester group, an amide group, or a sulfone group.

14. A pharmaceutical composition comprising a compound as claimed in claim 1 together with a pharmaceutically acceptable carrier.