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End-group modification of α-hydro-ω-methoxypoly(oxyethylene), 3. Facile methods for the introduction of a thiol-selective reactive end-group

✍ Scribed by Sabine Herman; Johan Loccufier; Etienne Schacht


Publisher
John Wiley and Sons
Year
1994
Tongue
English
Weight
372 KB
Volume
195
Category
Article
ISSN
1022-1352

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✦ Synopsis


Abstract

Three methods for the introduction of a thiol‐selective reactive end‐group into α‐hydro‐ω‐methoxypoly(oxyethylene) are described and evaluated. In a first method, α‐amino‐ω‐methoxypoly(oxyethylene) was reacted with succinimido 3‐(2‐pyridyldithio)propionate (SPDP). In a second approach, the hydroxyl end‐group of α‐hydro‐ω‐methoxypoly(oxyethylene) was activated with 4‐nitrophenyl chloroformate, and subsequently reacted with 2‐tritylthioethylamine. Conversion of the trityl thioether into an aromatic disulfide with 2‐nitrophenylsulfenyl chloride yielded a polymer with a thiol‐specific reactive disulfide end‐group. However, it was shown that dismutation in buffer medium does occur, what makes this approach less attractive. A third method involved the conversion of the trityl thioether into a sulfenyl thiocarbonate by reaction with an alkoxycarbonylsulfenyl chloride. Both the SPDP‐modified and the alkoxycarbonyl disulfide‐modified poly(oxyethylene) were found to be suitable thiol‐specific reactive polymers for protein modification. This was demonstrated in a model reaction using reduced glutathione as a thiol‐carrying peptide.