title: Screening of reducing agents for the PEGylation of recombinant human IL-10.
abstract: PEGylation is a technology commonly used to enhance the bioavailability of therapeutic proteins in patients. Reductive alkylation of a protein amino terminal alpha amine in the presence of a polyethylene glycol (PEG) chain derivatized with propionaldehyde and a reducing agent, typically sodium cyanoborohydride, is one of the technologies available to achieve quantitative and site specific PEGylation. While cyanoborohydride has proven to be a robust and efficient reagent for this type of reaction, it generates aqueous cyanide as a reaction by-product (and its corollary, the very volatile hydrogen cyanide). We report here the screening of reducing agents such as dimethylamine borane, trimethylamine borane, triethylamine borane, tert-butylamine borane, morpholine borane, pyridine borane, 2-picoline borane, and 5-ethyl-2-methyl-pyridine borane as alternatives to cyanoborohydride for the PEGylation of recombinant human IL-10. The results of our study show that pyridine borane and 2-picoline borane promote rhIL-10 PEGylation at levels comparable to those observed with cyanoborohydride.
authors: Bioprocess Development, Merck Research Laboratories, Union, NJ 07083-7197, USA. alexandre.ambrogelly@merck.com
authors: Alexandre
authors: A
authors: Ambrogelly
authors: Collette
authors: C
authors: Cutler
authors: Brittany
authors: B
authors: Paporello
mesh_terms: D004353:Drug Evaluation, Preclinical; D006801:Humans; D016753:Interleukin-10 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019163:Reducing Agents / Q000737:chemistry*
chemical_list: D011994:Recombinant Proteins; D019163:Reducing Agents; D016753:Interleukin-10; D011092:Polyethylene Glycols
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