Two-step activity-based protein profiling of diacylglycerol lipase

Eva J. Van Rooden; Roy Kreekel; Thomas Hansen; Antonius P.A. Janssen; Annelot C.M. Van Esbroeck; Hans Den Dulk; Richard J.B.H.N. Van Den Berg; Jeroen D.C. Codée; Mario Van Der Stelt

doi:10.1039/c8ob01499j

Two-step activity-based protein profiling of diacylglycerol lipase

Eva J. Van Rooden
, Roy Kreekel
, Thomas Hansen
, Antonius P.A. Janssen
, Annelot C.M. Van Esbroeck
, Hans Den Dulk
, Richard J.B.H.N. Van Den Berg
, Jeroen D.C. Codée
, Mario Van Der Stelt^*

^*Corresponding author for this work

Chemistry and Pharmaceutical Sciences

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Diacylglycerol lipases (DAGL) produce the endocannabinoid 2-arachidonoylglycerol, a key modulator of neurotransmitter release. Chemical tools that visualize endogenous DAGL activity are desired. Here, we report the design, synthesis and application of a triazole urea probe for DAGL equipped with a norbornene as a biorthogonal handle. The activity and selectivity of the probe was assessed with activity-based protein profiling. This probe was potent against endogenous DAGLα (IC₅₀ = 5 nM) and it was successfully applied as a two-step activity-based probe for labeling of DAGLα using an inverse electron-demand Diels-Alder ligation in living cells.

Original language	English
Pages (from-to)	5250-5253
Number of pages	4
Journal	Organic and Biomolecular Chemistry
Volume	16
Issue number	29
DOIs	https://doi.org/10.1039/c8ob01499j
Publication status	Published - 1 Jan 2018

Access to Document

10.1039/c8ob01499j

https://hdl.handle.net/1887/73948

Persistent URL (handle)

Persistent link

Cite this

@article{02d8004fdbb94b3f8992fcb04087fbda,

title = "Two-step activity-based protein profiling of diacylglycerol lipase",

abstract = "Diacylglycerol lipases (DAGL) produce the endocannabinoid 2-arachidonoylglycerol, a key modulator of neurotransmitter release. Chemical tools that visualize endogenous DAGL activity are desired. Here, we report the design, synthesis and application of a triazole urea probe for DAGL equipped with a norbornene as a biorthogonal handle. The activity and selectivity of the probe was assessed with activity-based protein profiling. This probe was potent against endogenous DAGLα (IC50 = 5 nM) and it was successfully applied as a two-step activity-based probe for labeling of DAGLα using an inverse electron-demand Diels-Alder ligation in living cells.",

author = "\{Van Rooden\}, \{Eva J.\} and Roy Kreekel and Thomas Hansen and Janssen, \{Antonius P.A.\} and \{Van Esbroeck\}, \{Annelot C.M.\} and \{Den Dulk\}, Hans and \{Van Den Berg\}, \{Richard J.B.H.N.\} and Cod{\'e}e, \{Jeroen D.C.\} and \{Van Der Stelt\}, Mario",

year = "2018",

month = jan,

day = "1",

doi = "10.1039/c8ob01499j",

language = "English",

volume = "16",

pages = "5250--5253",

journal = "Organic and Biomolecular Chemistry",

issn = "1477-0520",

publisher = "Royal Society of Chemistry",

number = "29",

}

TY - JOUR

T1 - Two-step activity-based protein profiling of diacylglycerol lipase

AU - Van Rooden, Eva J.

AU - Kreekel, Roy

AU - Hansen, Thomas

AU - Janssen, Antonius P.A.

AU - Van Esbroeck, Annelot C.M.

AU - Den Dulk, Hans

AU - Van Den Berg, Richard J.B.H.N.

AU - Codée, Jeroen D.C.

AU - Van Der Stelt, Mario

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Diacylglycerol lipases (DAGL) produce the endocannabinoid 2-arachidonoylglycerol, a key modulator of neurotransmitter release. Chemical tools that visualize endogenous DAGL activity are desired. Here, we report the design, synthesis and application of a triazole urea probe for DAGL equipped with a norbornene as a biorthogonal handle. The activity and selectivity of the probe was assessed with activity-based protein profiling. This probe was potent against endogenous DAGLα (IC50 = 5 nM) and it was successfully applied as a two-step activity-based probe for labeling of DAGLα using an inverse electron-demand Diels-Alder ligation in living cells.

AB - Diacylglycerol lipases (DAGL) produce the endocannabinoid 2-arachidonoylglycerol, a key modulator of neurotransmitter release. Chemical tools that visualize endogenous DAGL activity are desired. Here, we report the design, synthesis and application of a triazole urea probe for DAGL equipped with a norbornene as a biorthogonal handle. The activity and selectivity of the probe was assessed with activity-based protein profiling. This probe was potent against endogenous DAGLα (IC50 = 5 nM) and it was successfully applied as a two-step activity-based probe for labeling of DAGLα using an inverse electron-demand Diels-Alder ligation in living cells.

UR - https://www.scopus.com/pages/publications/85050653562

UR - https://www.scopus.com/pages/publications/85050653562#tab=citedBy

U2 - 10.1039/c8ob01499j

DO - 10.1039/c8ob01499j

M3 - Article

C2 - 30004552

AN - SCOPUS:85050653562

SN - 1477-0520

VL - 16

SP - 5250

EP - 5253

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 29

ER -

Two-step activity-based protein profiling of diacylglycerol lipase

Abstract

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Cite this