Loading…

Human Serum Albumin Domain I Fusion Protein for Antibody Conjugation

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 demonstr...

Full description

Saved in:
Bibliographic Details
Published in:Bioconjugate chemistry 2016-10, Vol.27 (10), p.2271-2275
Main Authors: Patterson, James T, Wilson, Henry D, Asano, Shigehiro, Nilchan, Napon, Fuller, Roberta P, Roush, William R, Rader, Christoph, Barbas, Carlos F
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.6b00432