Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2

Research output: Contribution to journalJournal article

Standard

Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid : a novel selective inhibitor of human excitatory amino acid transporter subtype 2. / Sagot, Emanuelle; Jensen, Anders A.; Pickering, Darryl S; Pu, Xiaosui; Umberti, Michelle; Stensbøl, Tine B.; Nielsen, Birgitte; Assaf, Zeinab; Aboab, Bétina; Bolte, Jean; Gefflaut, Thierry; Bunch, Lennart.

In: Journal of Medicinal Chemistry, Vol. 51, No. 14, 2008, p. 4085-4092.

Research output: Contribution to journalJournal article

Harvard

Sagot, E, Jensen, AA, Pickering, DS, Pu, X, Umberti, M, Stensbøl, TB, Nielsen, B, Assaf, Z, Aboab, B, Bolte, J, Gefflaut, T & Bunch, L 2008, 'Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2', Journal of Medicinal Chemistry, vol. 51, no. 14, pp. 4085-4092. https://doi.org/10.1021/jm800091e

APA

Sagot, E., Jensen, A. A., Pickering, D. S., Pu, X., Umberti, M., Stensbøl, T. B., ... Bunch, L. (2008). Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2. Journal of Medicinal Chemistry, 51(14), 4085-4092. https://doi.org/10.1021/jm800091e

Vancouver

Sagot E, Jensen AA, Pickering DS, Pu X, Umberti M, Stensbøl TB et al. Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2. Journal of Medicinal Chemistry. 2008;51(14):4085-4092. https://doi.org/10.1021/jm800091e

Author

Sagot, Emanuelle ; Jensen, Anders A. ; Pickering, Darryl S ; Pu, Xiaosui ; Umberti, Michelle ; Stensbøl, Tine B. ; Nielsen, Birgitte ; Assaf, Zeinab ; Aboab, Bétina ; Bolte, Jean ; Gefflaut, Thierry ; Bunch, Lennart. / Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid : a novel selective inhibitor of human excitatory amino acid transporter subtype 2. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 14. pp. 4085-4092.

Bibtex

@article{a0df6df0621711dd8d9f000ea68e967b,
title = "Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid: a novel selective inhibitor of human excitatory amino acid transporter subtype 2",
abstract = "In the mammalian central nervous system (CNS), the action of sodium dependent excitatory amino acid transporters (EAATs) is responsible for termination of glutamatergic neurotransmission by reuptake of ( S) -glutamate (Glu) from the synaptic cleft. Five EAAT subtypes have been identified, of which EAAT1-4 are present in the CNS, while EAAT5 is localized exclusively in the retina. In this study, we have used an enantioselective chemo-enzymatic strategy to synthesize 10 new Glu analogues 2a- k ( 2d is exempt) with different functionalities in the 4 R-position and characterized their pharmacological properties at the human EAAT1-3. In particular, one compound, 2k, displayed a significant preference as inhibitor of the EAAT2 subtype over EAAT1,3. The compound also displayed very low affinities toward ionotropic and metabotropic Glu receptors, making it the most selective EAAT2 inhibitor described so far.",
keywords = "Cell Line, Excitatory Amino Acid Antagonists, Glutamate Plasma Membrane Transport Proteins, Glutarates, Humans, Magnetic Resonance Spectroscopy, Membrane Potentials, Spectrometry, Mass, Electrospray Ionization, Stereoisomerism",
author = "Emanuelle Sagot and Jensen, {Anders A.} and Pickering, {Darryl S} and Xiaosui Pu and Michelle Umberti and Stensb{\o}l, {Tine B.} and Birgitte Nielsen and Zeinab Assaf and B{\'e}tina Aboab and Jean Bolte and Thierry Gefflaut and Lennart Bunch",
year = "2008",
doi = "10.1021/jm800091e",
language = "English",
volume = "51",
pages = "4085--4092",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "14",

}

RIS

TY - JOUR

T1 - Chemo-enzymatic synthesis of (2S,4R)-2-amino-4-(3-(2,2-diphenylethylamino)-3-oxopropyl)pentanedioic acid

T2 - a novel selective inhibitor of human excitatory amino acid transporter subtype 2

AU - Sagot, Emanuelle

AU - Jensen, Anders A.

AU - Pickering, Darryl S

AU - Pu, Xiaosui

AU - Umberti, Michelle

AU - Stensbøl, Tine B.

AU - Nielsen, Birgitte

AU - Assaf, Zeinab

AU - Aboab, Bétina

AU - Bolte, Jean

AU - Gefflaut, Thierry

AU - Bunch, Lennart

PY - 2008

Y1 - 2008

N2 - In the mammalian central nervous system (CNS), the action of sodium dependent excitatory amino acid transporters (EAATs) is responsible for termination of glutamatergic neurotransmission by reuptake of ( S) -glutamate (Glu) from the synaptic cleft. Five EAAT subtypes have been identified, of which EAAT1-4 are present in the CNS, while EAAT5 is localized exclusively in the retina. In this study, we have used an enantioselective chemo-enzymatic strategy to synthesize 10 new Glu analogues 2a- k ( 2d is exempt) with different functionalities in the 4 R-position and characterized their pharmacological properties at the human EAAT1-3. In particular, one compound, 2k, displayed a significant preference as inhibitor of the EAAT2 subtype over EAAT1,3. The compound also displayed very low affinities toward ionotropic and metabotropic Glu receptors, making it the most selective EAAT2 inhibitor described so far.

AB - In the mammalian central nervous system (CNS), the action of sodium dependent excitatory amino acid transporters (EAATs) is responsible for termination of glutamatergic neurotransmission by reuptake of ( S) -glutamate (Glu) from the synaptic cleft. Five EAAT subtypes have been identified, of which EAAT1-4 are present in the CNS, while EAAT5 is localized exclusively in the retina. In this study, we have used an enantioselective chemo-enzymatic strategy to synthesize 10 new Glu analogues 2a- k ( 2d is exempt) with different functionalities in the 4 R-position and characterized their pharmacological properties at the human EAAT1-3. In particular, one compound, 2k, displayed a significant preference as inhibitor of the EAAT2 subtype over EAAT1,3. The compound also displayed very low affinities toward ionotropic and metabotropic Glu receptors, making it the most selective EAAT2 inhibitor described so far.

KW - Cell Line

KW - Excitatory Amino Acid Antagonists

KW - Glutamate Plasma Membrane Transport Proteins

KW - Glutarates

KW - Humans

KW - Magnetic Resonance Spectroscopy

KW - Membrane Potentials

KW - Spectrometry, Mass, Electrospray Ionization

KW - Stereoisomerism

U2 - 10.1021/jm800091e

DO - 10.1021/jm800091e

M3 - Journal article

C2 - 18578477

VL - 51

SP - 4085

EP - 4092

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 14

ER -

ID: 5345305