The collection of chemical techniques that can be used to attach synthetic groups to proteins has expanded substantially in recent years. Each of these approaches allows new protein targets to be addressed, leading to advances in biological understanding, new protein-drug conjugates, targeted medical imaging agents and hybrid materials with complex functions. The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. Some are more amenable to large-scale bioconjugate production, and a number of techniques can be used to label a single protein in a complex biological mixture. This review examines the way in which experimental circumstances influence one's selection of an appropriate protein modification strategy. It also provides a simple decision tree that can narrow down the possibilities in many instances. The review concludes with example studies that examine how this decision process has been applied in different contexts.
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Our efforts to develop new bioconjugation strategies, capsid-based delivery agents, and proteinpolymer hybrid materials have been generously supported by the US National Institutes of Health (GM072700), the Department of Defense Breast Cancer Research Program (BC061995) and the US National Science Foundation (0449772). While writing this manuscript, N.S. was supported by the Director of the Office of Science, Materials Sciences and Engineering Division, US Department of Energy under contract no. DE-AC02-05CH11231.
The authors declare no competing financial interests.
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Stephanopoulos, N., Francis, M. Choosing an effective protein bioconjugation strategy. Nat Chem Biol 7, 876–884 (2011). https://doi.org/10.1038/nchembio.720
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