Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 53, Issue 34, Pages 9045-9050Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201404622
Keywords
deoxyribozymes; DNA; in vitro selection; lysine modification; peptides
Categories
Funding
- National Institutes of Health [R01GM065966]
- Defense Threat Reduction Agency [HDTRA1-09-1-0011]
- National Science Foundation [CHE0842534]
- NIH [T32GM070421]
Ask authors/readers for more resources
Catalyzing the covalent modification of aliphatic amino groups, such as the lysine (Lys) side chain, by nucleic acids has been challenging to achieve. Such catalysis will be valuable, for example, for the practical preparation of Lysmodified proteins. We previously reported the DNA-catalyzed modification of the tyrosine and serine hydroxy side chains, but Lys modification has been elusive. Herein, we show that increasing the reactivity of the electrophilic reaction partner by using 5'-phosphorimidazolide (5'-Imp) rather than 5'-triphosphate (5'-ppp) enables the DNA-catalyzed modification of Lys in a DNA-anchored peptide substrate. The DNA-catalyzed reaction of Lys with 5'-Imp is observed in an architecture in which the nucleophile and electrophile are not preorganized. In contrast, previous efforts showed that catalysis was not observed when Lys and 5'-ppp were used in a preorganized arrangement. Therefore, substrate reactivity is more important than preorganization in this context. These findings will assist ongoing efforts to identify DNA catalysts for reactions of protein substrates at lysine side chains.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available