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Human Serum Albumin Domain I Fusion Protein for Antibody Conjugation.


ABSTRACT: Bioorthogonal labeling of antibodies enables the conjugation of compounds, such as small molecules or peptides, which expand targeting capacity or enhance cytotoxicity. Taking advantage of a cyclohexene sulfonamide compound that site-selectively labels Lys64 in human serum albumin (HSA), we demonstrate that domain I of HSA can be used as a fusion protein for the preparation of antibody conjugates. Trastuzumab fusions were expressed at the N-terminus of the light chain or the C-terminus of the heavy chain enabling conjugation to small molecules. Moreover, these conjugates retained HER2 binding and proved to be highly stable in human plasma. Antibody conjugation via HSA domain I fusion should therefore have broad utility for making serum-stable antibody conjugates, particularly for antibody-drug conjugates.

SUBMITTER: Patterson JT 

PROVIDER: S-EPMC5367151 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Human Serum Albumin Domain I Fusion Protein for Antibody Conjugation.

Patterson James T JT   Wilson Henry D HD   Asano Shigehiro S   Nilchan Napon N   Fuller Roberta P RP   Roush William R WR   Rader Christoph C   Barbas Carlos F CF  

Bioconjugate chemistry 20160926 10


Bioorthogonal labeling of antibodies enables the conjugation of compounds, such as small molecules or peptides, which expand targeting capacity or enhance cytotoxicity. Taking advantage of a cyclohexene sulfonamide compound that site-selectively labels Lys64 in human serum albumin (HSA), we demonstrate that domain I of HSA can be used as a fusion protein for the preparation of antibody conjugates. Trastuzumab fusions were expressed at the N-terminus of the light chain or the C-terminus of the he  ...[more]

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