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Site-specific PEGylation reagents have been developed that undergo thiol-specific bis-alkylation with the two cysteine sulphur atoms from a native accessible disulphide in proteins. The process for this approach of site-specific PEGylation involves two steps: (1) disulphide reduction to release the two thiols and (2) bis-alkylation of the PEG reagent to the two sulphur atoms to give a three-carbon...
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