- Switching Lysophosphatidylserine G Protein-Coupled Receptor Agonists to Antagonists by Acylation of the Hydrophilic Serine Amine
-
Three human G protein-coupled receptors (GPCRs)—GPR34/LPS1, P2Y10/LPS2, and GPR174/LPS3—are activated specifically by lysophosphatidylserine (LysoPS), an endogenous hydrolysis product of a cell membrane component, phosphatidylserine (PS). LysoPS consists of-serine, glycerol, and fatty acid moieties connected by phosphodiester and ester linkages. We previously generated potent and selective GPCR agonists by modification of the three modules and the ester linkage. Here, we show that a novel modification of the hydrophilic serine moiety, that is, N-acylations of the serine amine, converted a GPR174 agonist to potent GPR174 antagonists. Structural exploration of the amide functionality provided access to a range of activities from agonist to partial agonist to antagonist. The present study would provide a new strategy for the development of lysophospholipid receptor antagonists.
- Sayama, Misa,Uwamizu, Akiharu,Ikubo, Masaya,Chen, Luying,Yan, Ge,Otani, Yuko,Inoue, Asuka,Aoki, Junken,Ohwada, Tomohiko
-
p. 10059 - 10101
(2021/07/28)
-
- Stable triazolylphosphonate analogues of phosphohistidine
-
Histidine-phosphorylated proteins and the corresponding kinases are important components of bacterial and eukaryotic cell-signalling pathways, and are therefore potential drug targets. The study of these biomolecules has been hampered by the lability of the phosphoramidate functional group in the phosphohistidines and the lack of generic antibodies. Herein, the design and concise synthesis of stable triazolylphosphonate analogues of N1-and N3-phosphohistidine, and derivatives suitable for bioconjugation, are described. Springer-Verlag 2011.
- Mukai, Shin,Flematti, Gavin R.,Byrne, Lindsay T.,Besant, Paul G.,Attwood, Paul V.,Piggott, Matthew J.
-
experimental part
p. 857 - 874
(2012/10/07)
-
- Vinyl carboxylate an acylating reagent for selective acylation of amines and diols
-
Vinyl group of vinyl alkylate (C=2 or 16) and vinyl benzoate have been found to be a good leaving group in acylation of alcohols (40-50% yield) and amines (in 60-90% yield).
- Chen,Chen,Chen,Wang
-
p. 3583 - 3584
(2007/10/02)
-