Hydroxamic Acid‐Piperidine Conjugate is an Activated Catalyst for Lysine Acetylation under Physiological Conditions. Issue 6 (19th February 2020)

• Record Type: Journal Article
• Authors: Mizumoto, Shinsuke; Xi, Siqi; Fujiwara, Yusuke; Kawashima, Shigehiro A.; Yamatsugu, Kenzo; Kanai, Motomu
• Is Part Of: Chemistry, an Asian journal. Volume 15:Issue 6(2020)
• Page Start: 833
• Page End: 839
• Publication Date: 2020-02-19
• Subjects: acylation -- catalyst -- hydroxamic acid -- lysine acetylation -- protein modifications; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/asia.201901737
• Languages: English
• ISSNs: 1861-4728

Abstract

Abstract: Lysine acylation of proteins is an essential chemical reaction for posttranslational modification and as a means of protein modification in various applications. N, N ‐Dimethyl‐4‐aminopyridine (DMAP) derivatives are widely‐used catalysts for lysine acylation of proteins; however, the DMAP moiety mostly exists in a protonated, and thus deactivated, form under physiological conditions due to its basicity. An alternative catalytic motif furnishing higher acylation activity would further broaden the possible applications of chemical lysine acylation. We herein report that the hydroxamic acid‐piperidine conjugate Ph‐HXA is a more active catalytic motif for lysine acetylation than DMAP under physiological conditions. In contrast to DMAP, the hydroxamic acid moiety is mostly deprotonated under aqueous neutral pH, resulting in a higher concentration of the activated form. The Ph‐HXA catalyst is also more tolerant of deactivation by a high concentration of glutathione than DMAP. Therefore, Ph‐HXA might be a suitable catalytic motif for target protein‐selective and site‐selective acetylation in cells. Abstract : A hydroxamic acid‐piperidine conjugate is a superior lysine acetylation catalyst for protein modifications to N, N ‐dimethyl‐4‐aminopyridine (DMAP). It is activated through deprotonation under physiological conditions, and is less susceptible to inactivation by glutathione.