Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups. / Christensen, Søren Brøgger; Andersen, Annette; Poulsen, Jens Christian J.; Treiman, Marek.

In: FEBS Letters, Vol. 335, No. 3, 13.12.1993, p. 345-348.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Christensen, SB, Andersen, A, Poulsen, JCJ & Treiman, M 1993, 'Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups', FEBS Letters, vol. 335, no. 3, pp. 345-348. https://doi.org/10.1016/0014-5793(93)80416-R

APA

Christensen, S. B., Andersen, A., Poulsen, J. C. J., & Treiman, M. (1993). Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups. FEBS Letters, 335(3), 345-348. https://doi.org/10.1016/0014-5793(93)80416-R

Vancouver

Christensen SB, Andersen A, Poulsen JCJ, Treiman M. Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups. FEBS Letters. 1993 Dec 13;335(3):345-348. https://doi.org/10.1016/0014-5793(93)80416-R

Author

Christensen, Søren Brøgger ; Andersen, Annette ; Poulsen, Jens Christian J. ; Treiman, Marek. / Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups. In: FEBS Letters. 1993 ; Vol. 335, No. 3. pp. 345-348.

Bibtex

@article{ff6c46e9ceb9450cb81edf806e53495e,
title = "Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups",
abstract = "The naturally occurring sesquiterpene lactone thapsigargin is a potent and selective inhibitor of SERCA ATPases, a family of Ca2+-pumping ATPases present in the endoplasmic reticulum of all mammalian cells. We have studied some of the molecular features of thapsigargin responsible for its inhibitory action towards these Ca2+ ATPases. A series of thapsigargin analogues were synthesised and their inhibitory potencies determined using the uptake of 45Ca2+ in bovine cerebellar microsomes as a sensitive marker of Ca2+ ATPase activity. An attenuation of the inhibitory potency relative to the parent compound was found ranging from slight to over 3 orders of magnitude. The inhibitory activity showed a very strong configuration dependence, a major contribution from the ester groups at C3 and C10, and an apparently minor contribution from the lactone ring substituents. The data are consistent with thapsigargin fitting to a sterically discriminating cleft involving the hydrophobic transmembrane region of the ATPase, and is compatible with available kinetic evidence of thapsigargin-mediated inhibition.",
keywords = "Ca ATPase, Ca store, Endoplasmic reticulum, Thapsigargin",
author = "Christensen, {S{\o}ren Br{\o}gger} and Annette Andersen and Poulsen, {Jens Christian J.} and Marek Treiman",
year = "1993",
month = dec,
day = "13",
doi = "10.1016/0014-5793(93)80416-R",
language = "English",
volume = "335",
pages = "345--348",
journal = "F E B S Letters",
issn = "0014-5793",
publisher = "JohnWiley & Sons Ltd",
number = "3",

}

RIS

TY - JOUR

T1 - Derivatives of thapsigargin as probes of its binding site on endoplasmic reticulum Ca2+ ATPase. Stereoselectivity and important functional groups

AU - Christensen, Søren Brøgger

AU - Andersen, Annette

AU - Poulsen, Jens Christian J.

AU - Treiman, Marek

PY - 1993/12/13

Y1 - 1993/12/13

N2 - The naturally occurring sesquiterpene lactone thapsigargin is a potent and selective inhibitor of SERCA ATPases, a family of Ca2+-pumping ATPases present in the endoplasmic reticulum of all mammalian cells. We have studied some of the molecular features of thapsigargin responsible for its inhibitory action towards these Ca2+ ATPases. A series of thapsigargin analogues were synthesised and their inhibitory potencies determined using the uptake of 45Ca2+ in bovine cerebellar microsomes as a sensitive marker of Ca2+ ATPase activity. An attenuation of the inhibitory potency relative to the parent compound was found ranging from slight to over 3 orders of magnitude. The inhibitory activity showed a very strong configuration dependence, a major contribution from the ester groups at C3 and C10, and an apparently minor contribution from the lactone ring substituents. The data are consistent with thapsigargin fitting to a sterically discriminating cleft involving the hydrophobic transmembrane region of the ATPase, and is compatible with available kinetic evidence of thapsigargin-mediated inhibition.

AB - The naturally occurring sesquiterpene lactone thapsigargin is a potent and selective inhibitor of SERCA ATPases, a family of Ca2+-pumping ATPases present in the endoplasmic reticulum of all mammalian cells. We have studied some of the molecular features of thapsigargin responsible for its inhibitory action towards these Ca2+ ATPases. A series of thapsigargin analogues were synthesised and their inhibitory potencies determined using the uptake of 45Ca2+ in bovine cerebellar microsomes as a sensitive marker of Ca2+ ATPase activity. An attenuation of the inhibitory potency relative to the parent compound was found ranging from slight to over 3 orders of magnitude. The inhibitory activity showed a very strong configuration dependence, a major contribution from the ester groups at C3 and C10, and an apparently minor contribution from the lactone ring substituents. The data are consistent with thapsigargin fitting to a sterically discriminating cleft involving the hydrophobic transmembrane region of the ATPase, and is compatible with available kinetic evidence of thapsigargin-mediated inhibition.

KW - Ca ATPase

KW - Ca store

KW - Endoplasmic reticulum

KW - Thapsigargin

UR - http://www.scopus.com/inward/record.url?scp=0027366716&partnerID=8YFLogxK

U2 - 10.1016/0014-5793(93)80416-R

DO - 10.1016/0014-5793(93)80416-R

M3 - Journal article

C2 - 8262181

AN - SCOPUS:0027366716

VL - 335

SP - 345

EP - 348

JO - F E B S Letters

JF - F E B S Letters

SN - 0014-5793

IS - 3

ER -

ID: 232597980