Conjugated biological molecules and their preparation

A process for the preparation of a compound of the general formula: in which one of X and X' represents polyethylene glycol, and the other represents a hydrogen atom; each Q independently represents a linking group; W represents a keto group CO, an ester group -O-CO- or a sulphone group -SO 2 -, or a group obtained by reduction of such a group; or, if X' represents polyethylene glycol, X-Q-W-together represent a cyano group; Z represents a protein which is linked to A and B via two thiol groups which have been derived from a disulphide bridge in the protein; A is a C 1-5 alkylene or alkenylene chain; and B is a bond or a C 1-4 alkylene or alkenylene chain; which comprises reducing a disulfide bridge in a protein, and reacting the resultant product in an aqueous reaction medium with either (i) a compound of the general formula in which X, X', Q, A, B and L have the meanings given above, W' represents a keto or aldehyde group CO, an ester group -O-CO- or a sulphone group -SO 2 -, and each L independently represents a leaving group; or (ii) a compound of the general formula in which X, X', Q, W', A and L have the meanings given for the general formula II, and m represents an integer 1 to 4. Also claimed is novel intermediate ±-methoxy-É-4-[2,2-bis[(p-tolylsulfonyl)methyl]-acetyl]benzamide poly(ethylene glycol).