Polymeric alpha-hydroxy aldehyde and ketone reagents and conjugation method

Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functiona...

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Hauptverfasser: Shen, Xiaoming, McManus, Samuel P, Kozlowski, Antoni, Culbertson, Sean M
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creator Shen, Xiaoming
McManus, Samuel P
Kozlowski, Antoni
Culbertson, Sean M
description Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.
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In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. 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subjects CHEMISTRY
COMPOSITIONS BASED THEREON
COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
HUMAN NECESSITIES
HYGIENE
MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONSONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
MEDICAL OR VETERINARY SCIENCE
METALLURGY
ORGANIC CHEMISTRY
ORGANIC MACROMOLECULAR COMPOUNDS
PEPTIDES
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
THEIR PREPARATION OR CHEMICAL WORKING-UP
title Polymeric alpha-hydroxy aldehyde and ketone reagents and conjugation method
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