Organic Letters
Letter
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addition, 2,4-thiazolinedione (3a) was proved to be relatively
safe to 3T3 and LO2 cells even at high concentration (Table
S2, Supporting Information), which indicated that the aldol
ligation has potential for application inside the cells.
In conclusion, we have described the first direct aldol
reaction that could be applied for site-specific chemical
modification of an aldehyde-containing protein. N-Substituted
2,4-thiazolidinediones could selectively form a stable C−C
bond with an aldehyde-containing protein under moderate
conditions and thereby introduce diverse functional groups
including azide, olefin, and bromide into protein without
changing its native conformation. This direct aldol ligation may
offer a potential bioorthogonal reaction for functionalization of
protein.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental details and characterization data for all new
compounds. This material is available free of charge via the
AUTHOR INFORMATION
■
Corresponding Authors
Notes
The authors declare no competing financial interest.
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der Weijden, J.; Sletten, E. M.; Rabuka, D.; Bertozzi, C. R. Proc. Natl.
Acad. Sci. U.S.A. 2013, 110, 46−51.
ACKNOWLEDGMENTS
■
This work was supported by the National Basic Research
Program of China (973 program, Grant No. 2013CB911104),
the National Natural Science Foundation of China (Grant No.
21202087), the Tianjin Science and Technology Program
(Grant No. 13JCYBJC24300, 13JCQNJC13100), and the “111”
Project of the Ministry of Education of China (Project No.
B06005). We sincerely thank Ms. Zhongyuan Sun of Protein
Chemistry Facility, Center of Biomedical Analysis, Tsinghua
University, for the service of the trypsin digestion analysis and
Dr. Yaxin Lu, Ms. Man Wang of Nankai University, and Dr.
Peiming Gu of Thermo Fisher Scientific for the service of the
LC−ESI-Orbitrap MS analysis.
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