In:
ChemBioChem, Wiley, Vol. 19, No. 8 ( 2018-04-16), p. 799-804
Abstract:
Activated esters are widely used to label proteins at lysine side chains and N termini. These reagents are useful for labeling virtually any protein, but robust reactivity toward primary amines generally precludes site‐selective modification. In a unique case, fluorophenyl esters are shown to preferentially label human kappa antibodies at a single lysine (Lys188) within the light‐chain constant domain. Neighboring residues His189 and Asp151 contribute to the accelerated rate of labeling at Lys188 relative to the ≈40 other lysine sites. Enriched Lys188 labeling can be enhanced from 50–70 % to 〉 95 % by any of these approaches: lowering reaction temperature, applying flow chemistry, or mutagenesis of specific residues in the surrounding protein environment. Our results demonstrated that activated esters with fluoro‐substituted aromatic leaving groups, including a fluoronaphthyl ester, can be generally useful reagents for site‐selective lysine labeling of antibodies and other immunoglobulin‐type proteins.
Type of Medium:
Online Resource
ISSN:
1439-4227
,
1439-7633
DOI:
10.1002/cbic.201700611
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2020469-3
SSG:
12
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