PMID- 29732068
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2041-6520 (Print)
IS  - 2041-6539 (Electronic)
IS  - 2041-6520 (Linking)
VI  - 9
IP  - 10
DP  - 2018 Mar 14
TI  - Chemical proteomic profiling of protein N-homocysteinylation with a thioester 
      probe.
PG  - 2826-2830
LID - 10.1039/c8sc00221e [doi]
AB  - Hyperhomocysteinemia (HHcy) refers to a medical condition of abnormally high 
      level of homocysteine (Hcy) in blood (>15 mumol L(-1)) and has been clinically 
      implicated with cardiovascular diseases and neurodegenerative disorders. 
      Excessive Hcy can be converted to a reactive thioester intermediate, Hcy 
      thiolactone (HTL), which selectively reacts with protein lysine residues 
      ("N-homocysteinylation") and this non-enzymatic modification largely contributes 
      to manifestations of HHcy. However, the proteome-wide detection of protein 
      N-homocysteinylation remains a challenge to date. In this work, we report a 
      chemoselective reaction to label and enrich N-homocysteinylation from complex 
      proteome samples as inspired by native chemical ligation for protein synthesis. 
      Alkynyl thioester probes are synthesized and the reaction is validated with small 
      molecule and purified protein models successfully. We performed quantitative 
      chemical proteomics to identify more than 800 N-homocysteinylated proteins as 
      well as 304 N-homocysteinylated sites directly from HTL-treated HeLa cells. The 
      chemical proteomics strategies will facilitate functional study of protein 
      N-homocysteinylations in the HHcy-implicated diseases.
FAU - Chen, Nan
AU  - Chen N
AUID- ORCID: 0000-0002-1313-2155
AD  - Synthetic and Functional Biomolecules Center , Beijing National Laboratory for 
      Molecular Sciences , Key Laboratory of Bioorganic Chemistry and Molecular 
      Engineering of Ministry of Education , College of Chemistry and Molecular 
      Engineering , Peking University , Beijing , 100871 , China . Email: 
      chuwang@pku.edu.cn.
FAU - Liu, Jinmin
AU  - Liu J
AD  - Synthetic and Functional Biomolecules Center , Beijing National Laboratory for 
      Molecular Sciences , Key Laboratory of Bioorganic Chemistry and Molecular 
      Engineering of Ministry of Education , College of Chemistry and Molecular 
      Engineering , Peking University , Beijing , 100871 , China . Email: 
      chuwang@pku.edu.cn.
FAU - Qiao, Zeyu
AU  - Qiao Z
AD  - Synthetic and Functional Biomolecules Center , Beijing National Laboratory for 
      Molecular Sciences , Key Laboratory of Bioorganic Chemistry and Molecular 
      Engineering of Ministry of Education , College of Chemistry and Molecular 
      Engineering , Peking University , Beijing , 100871 , China . Email: 
      chuwang@pku.edu.cn.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Synthetic and Functional Biomolecules Center , Beijing National Laboratory for 
      Molecular Sciences , Key Laboratory of Bioorganic Chemistry and Molecular 
      Engineering of Ministry of Education , College of Chemistry and Molecular 
      Engineering , Peking University , Beijing , 100871 , China . Email: 
      chuwang@pku.edu.cn.
FAU - Yang, Yue
AU  - Yang Y
AD  - Department of Physiology and Pathophysiology , School of Basic Medical Sciences , 
      Peking University , Beijing , 100191 , China.
FAU - Jiang, Changtao
AU  - Jiang C
AD  - Department of Physiology and Pathophysiology , School of Basic Medical Sciences , 
      Peking University , Beijing , 100191 , China.
FAU - Wang, Xian
AU  - Wang X
AD  - Department of Physiology and Pathophysiology , School of Basic Medical Sciences , 
      Peking University , Beijing , 100191 , China.
FAU - Wang, Chu
AU  - Wang C
AUID- ORCID: 0000-0002-6925-1268
AD  - Synthetic and Functional Biomolecules Center , Beijing National Laboratory for 
      Molecular Sciences , Key Laboratory of Bioorganic Chemistry and Molecular 
      Engineering of Ministry of Education , College of Chemistry and Molecular 
      Engineering , Peking University , Beijing , 100871 , China . Email: 
      chuwang@pku.edu.cn.
AD  - Peking-Tsinghua Center for Life Sciences , Peking University , Beijing , 100871 , 
      China.
LA  - eng
PT  - Journal Article
DEP - 20180216
PL  - England
TA  - Chem Sci
JT  - Chemical science
JID - 101545951
PMC - PMC5914431
EDAT- 2018/05/08 06:00
MHDA- 2018/05/08 06:01
PMCR- 2018/02/16
CRDT- 2018/05/08 06:00
PHST- 2018/01/15 00:00 [received]
PHST- 2018/02/13 00:00 [accepted]
PHST- 2018/05/08 06:00 [entrez]
PHST- 2018/05/08 06:00 [pubmed]
PHST- 2018/05/08 06:01 [medline]
PHST- 2018/02/16 00:00 [pmc-release]
AID - c8sc00221e [pii]
AID - 10.1039/c8sc00221e [doi]
PST - epublish
SO  - Chem Sci. 2018 Feb 16;9(10):2826-2830. doi: 10.1039/c8sc00221e. eCollection 2018 
      Mar 14.