Biodegradable polyethylene glycol derivative having cyclic benzylidene acetal linker
AssigneeNof Corporation
InventorsTakuma Tsubusaki, Yuji Yamamoto
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Abstract
A biodegradable polyethylene glycol derivative in which a polyethylene glycol chain is linked by an acetal linker capable of accurately controlling the hydrolysis rate under different pH environments in the living body, and whose division rate into a polyethylene glycol chain of low molecular weight in the living body can be accurately controlled. The biodegradable polyethylene glycol derivative is represented by formula (1) or formula (2) as described.
Claims21
A method for chemical modification of a biofunctional molecule with a biodegradable polyethylene glycol compound having a cyclic benzylidene acetal linker for improving in vivo and intracellular kinetics in environments having different pH in a living body, which comprises reacting a functional group in the biofunctional molecule with a chemically reactive functional group in the biodegradable polyethylene glycol compound having a cyclic benzylidene acetal linker,
- wherein the biodegradable polyethylene glycol compound having a cyclic benzylidene acetal linker is represented by formula (1) or formula (2):
- wherein, in the formula (1) and the formula (2), R1 and R6 are each independently a hydrogen atom or a hydrocarbon group;
- R2, R3, R4 and R5 are each independently an electron-withdrawing or electron-donating substituent or a hydrogen atom;
- s is 1 or 2, t is 0 or 1, and s+t is 1 or 2;
- P1 is a straight-chain or branched polyethylene glycol having a number of ethylene glycol units of 3 or more;
- P2 is a straight-chain or branched polyethylene glycol having a number of ethylene glycol units of 3 or more;
- w is an integer of 1 to 8;
- u is an integer of 1 to 40;
- v is an integer of 1 to 4;
- X1 is the chemically reactive functional group and is selected from the group consisting of an active ester group, an active carbonate group, an aldehyde group, an isocyanate group, an isothiocyanate group, an epoxy group, a maleimide group, a vinyl sulfone group, an acryl group, a sulfonyloxy group, a carboxy group, a thiol group, a dithiopyridyl group, an α-haloacetyl group, an alkynyl group, an allyl group, a vinyl group, an amino group, an oxyamino group, a hydrazide group and an azide group;
- and
- Z1, Z2 and Z3 are each independently a selected divalent spacer.
Dependencies are inferred from the claim text.