TY - JOUR
T1 - Thienyl-Substituted α-Ketoamide
T2 - A Less Hydrophobic Reactive Group for Photo-Affinity Labeling
AU - Ota, Eisuke
AU - Usui, Kazuteru
AU - Oonuma, Kana
AU - Koshino, Hiroyuki
AU - Nishiyama, Shigeru
AU - Hirai, Go
AU - Sodeoka, Mikiko
N1 - Funding Information:
The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Funding This work was partially supported by PRIME (Grant Number JP17gm5910018) and CREST (Grant Number JP17gm0710004) from the Japan Agency for Medical Research and development, AMED, JSPS KAKENHI (Grant Numbers 16H01167 in Middle Molecular Strategy and 15K12760), and RIKEN project funding. Notes The authors declare no competing financial interest.
PY - 2018/4/20
Y1 - 2018/4/20
N2 - Photoaffinity labeling (PAL) is an important tool in chemical biology research, but application of α-ketoamides for PAL has been hampered by their photoinstability. Here, we show that 2-thienyl-substituted α-ketoamide is a superior photoreactive group for PAL. Studies with a series of synthetic mannose-conjugated α-ketoamides revealed that 2-thienyl substitution of α-ketoamide decreased the electrophilicity of the keto group and reduced the rate of photodegradation. Mannose-conjugated thienyl α-ketoamide showed greater concanavalin A labeling efficiency than other alkyl or phenyl-substituted α-ketoamides. In comparison with representative conventional photoreactive groups, 2-thienyl ketoamide showed reduced labeling of nontarget proteins, probably owing to its lower hydrophobicity.
AB - Photoaffinity labeling (PAL) is an important tool in chemical biology research, but application of α-ketoamides for PAL has been hampered by their photoinstability. Here, we show that 2-thienyl-substituted α-ketoamide is a superior photoreactive group for PAL. Studies with a series of synthetic mannose-conjugated α-ketoamides revealed that 2-thienyl substitution of α-ketoamide decreased the electrophilicity of the keto group and reduced the rate of photodegradation. Mannose-conjugated thienyl α-ketoamide showed greater concanavalin A labeling efficiency than other alkyl or phenyl-substituted α-ketoamides. In comparison with representative conventional photoreactive groups, 2-thienyl ketoamide showed reduced labeling of nontarget proteins, probably owing to its lower hydrophobicity.
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U2 - 10.1021/acschembio.7b00988
DO - 10.1021/acschembio.7b00988
M3 - Article
C2 - 29457885
AN - SCOPUS:85045839226
VL - 13
SP - 876
EP - 880
JO - ACS Chemical Biology
JF - ACS Chemical Biology
SN - 1554-8929
IS - 4
ER -