Ontology type: schema:ScholarlyArticle Open Access: True
2016-11
AUTHORSSurojit Sur, Yuan Qiao, Anja Fries, Robert N O'Meally, Robert N Cole, Kenneth W Kinzler, Bert Vogelstein, Shibin Zhou
ABSTRACTChemical conjugation is commonly used to enhance the pharmacokinetics, biodistribution, and potency of protein therapeutics, but often leads to non-specific modification or loss of bioactivity. Here, we present a simple, versatile and widely applicable method that allows exquisite N-terminal specific modification of proteins. Combining reversible side-chain blocking and protease mediated cleavage of a commonly used HIS tag appended to a protein, we generate with high yield and purity exquisitely site specific and selective bio-conjugates of TNF-α by using amine reactive NHS ester chemistry. We confirm the N terminal selectivity and specificity using mass spectral analyses and show near complete retention of the biological activity of our model protein both in vitro and in vivo murine models. We believe that this methodology would be applicable to a variety of potentially therapeutic proteins and the specificity afforded by this technique would allow for rapid generation of novel biologics. More... »
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DOIhttp://dx.doi.org/10.1038/srep18363
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