Sialic acid derivatives for protein derivatisation and conjugation

A process according to any preceding claim in which the starting material is a di-, oligo- or poly-saccharide.

A process according to any preceding claim in which step a) is carried out under conditions such that pendent carboxyl groups on the starting material are not reduced.

A process according to any preceding claim in which the aldehyde derivative is reacted with a substrate having a primary amine group or a hydrazide group.

A compound which is an aldehyde derivative of a di-, oligo or poly-saccharide comprising at least one sialic acid unit, in which the terminal unit at the reducing end includes an aldehyde moiety or is a group OR, in which R is selected from

• —CH2CH2NHR1, CH2CH═N—NHR1 and CH2CH2NHNHR1 in which R1 is H, C1-24 alkyl, aryl C2-6 alkanoyl, or a polypeptide or a protein linked through the N terminal or the γ-amine group of a lysine residue, a drug delivery system or is an organic group having a functional substituent adapted for reaction with a sulfhydryl group.

A process in which a sialic acid starting material having a terminal sialic acid at a non-reducing terminal end is subjected to the following steps:

• c) a selective oxidation step to oxidise the non-reducing terminal sialic acid unit at the 7, 8 vicinal diol group to form a 7-aldehyde;
• and
• d) a reduction step to reduce the 7-aldehyde group to the corresponding alcohol.

A process according to any of claims 32 to 36 in which oxidation step (c) is carried out in aqueous solution in the presence of periodate at a concentration in the range 1 mM to 1M, a pH in the range 3 to 10, a temperature in the range 0 to 60° C. and a time in the range 1 min to 48 hours.

A process according to any of claims 32 to 37 in which the reduction step d) is carried out in aqueous solution in the presence of borohydride at a concentration in the range 1 μM to 0.1M, a pH in the range 6.5 to 10, a temperature in the range 0 to 60° C. and a period in the range 1 min to 48 h.