DNA‐Catalyzed Lysine Side Chain Modification

Abstract

Catalysis of covalent modification of aliphatic amine groups, such as the lysine (Lys) side chain, by nucleic acids has been challenging to achieve. Such catalysis will be valuable, e.g., for practical preparation of Lys-modified proteins. We previously reported DNA-catalyzed modification of the tyrosine and serine hydroxyl side chains, but Lys modification has been elusive. In this study, we show that increasing the reactivity of the electrophilic reaction partner by using 5′-phosphorimidazolide (5′-Imp) rather than 5′-triphosphate (5′-ppp) enables DNA-catalyzed modification of Lys in a DNA-anchored peptide substrate. DNA-catalyzed reaction of Lys + 5′-Imp is observed in an architecture in which the nucleophile and electrophile are not preorganized, whereas catalysis was not observed in our prior efforts that used Lys + 5′-ppp 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.

CN and NH Bond Metathesis Reactions Mediated by Carbon Dioxide

“…[6] For example, CO 2 generated from cellular respiration is expired in part through the reversible formation of ac arbamate between CO 2 and the amino groups of hemoglobin. [7] Furthermore, the reactions of primary and secondary amines with CO 2 are used to captureC O 2 through the formation of az witterion first and then ac arbamate.…”

DNA-catalyzed glycosylation using aryl glycoside donors

“…These observations indicate the need to improve our selection strategy to disallow the survival of DNA sequences that catalyze their own glycosylation rather than modification of the intended peptide substrate. In previous studies, we have initially found unanticipated DNA-catalyzed reactivity and then resolved the issue to achieve our initial goal; e.g., refs 13 and 14.…”

DNA Catalysis: The Chemical Repertoire of DNAzymes

“…( A ) General representation of DNAzyme catalyzed ligation reactions. A nucleophile (e.g., an RNA 2′-OH, a terminal 3′-OH, hydroxyl groups of serine and tyrosine, or an amine) located on a substrate attacks an electrophilic position (e.g., 5′-triphosphate, 5′-phosphorimidazolide) located on the second substrate with the concomitant eviction of a leaving group; ( B ) Catalyzed ligation reaction by hydrolysis of a phosphoramidate bond [162]; ( C ) DNAzyme catalyzed nucleophilic attack of an amine group of a lysine residue on a 5′-phosphorimidazolide unit [172]. …”