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Aberrant cyclization affords a C-6 modified cyclic adenosine 5'-diphosphoribose analogue with biological activity in Jurkat T cells.

Standard

Aberrant cyclization affords a C-6 modified cyclic adenosine 5'-diphosphoribose analogue with biological activity in Jurkat T cells. / Moreau, Christelle; Kirchberger, Tanja; Zhang, Bo; Thomas, Mark P; Weber, Karin; Guse, Andreas H.; Potter, Barry V L.

In: J MED CHEM, Vol. 55, No. 4, 4, 2012, p. 1478-1489.

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

Harvard

Moreau, C, Kirchberger, T, Zhang, B, Thomas, MP, Weber, K, Guse, AH & Potter, BVL 2012, 'Aberrant cyclization affords a C-6 modified cyclic adenosine 5'-diphosphoribose analogue with biological activity in Jurkat T cells.', J MED CHEM, vol. 55, no. 4, 4, pp. 1478-1489. <http://www.ncbi.nlm.nih.gov/pubmed/22248391?dopt=Citation>

APA

Moreau, C., Kirchberger, T., Zhang, B., Thomas, M. P., Weber, K., Guse, A. H., & Potter, B. V. L. (2012). Aberrant cyclization affords a C-6 modified cyclic adenosine 5'-diphosphoribose analogue with biological activity in Jurkat T cells. J MED CHEM, 55(4), 1478-1489. [4]. http://www.ncbi.nlm.nih.gov/pubmed/22248391?dopt=Citation

Vancouver

Moreau C, Kirchberger T, Zhang B, Thomas MP, Weber K, Guse AH et al. Aberrant cyclization affords a C-6 modified cyclic adenosine 5'-diphosphoribose analogue with biological activity in Jurkat T cells. J MED CHEM. 2012;55(4):1478-1489. 4.

Bibtex

@article{725336b0fa344defb7b2a6f0d3d8d918,
title = "Aberrant cyclization affords a C-6 modified cyclic adenosine 5'-diphosphoribose analogue with biological activity in Jurkat T cells.",
abstract = "Two nicotinamide adenine dinucleotide (NAD(+)) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD(+) (6-N-methyl nicotinamide adenosine 5'-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5'-diphosphoribose, 11), whereas 6-thio NHD(+) (nicotinamide 6-mercaptopurine 5'-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5'-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5'-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1-cIDPR-induced Ca(2+) release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5'-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1-cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling.",
keywords = "Animals, Humans, Models, Molecular, Permeability, Calcium/metabolism, Hydrogen-Ion Concentration, Jurkat Cells, Structure-Activity Relationship, Molecular Conformation, Cyclization, ADP-ribosyl Cyclase/chemistry, Aplysia, Cyclic ADP-Ribose/*analogs & derivatives/*chemical synthesis/pharmacology, T-Lymphocytes/*drug effects/metabolism, Thioinosine/*analogs & derivatives/chemical synthesis/pharmacology, Animals, Humans, Models, Molecular, Permeability, Calcium/metabolism, Hydrogen-Ion Concentration, Jurkat Cells, Structure-Activity Relationship, Molecular Conformation, Cyclization, ADP-ribosyl Cyclase/chemistry, Aplysia, Cyclic ADP-Ribose/*analogs & derivatives/*chemical synthesis/pharmacology, T-Lymphocytes/*drug effects/metabolism, Thioinosine/*analogs & derivatives/chemical synthesis/pharmacology",
author = "Christelle Moreau and Tanja Kirchberger and Bo Zhang and Thomas, {Mark P} and Karin Weber and Guse, {Andreas H.} and Potter, {Barry V L}",
year = "2012",
language = "English",
volume = "55",
pages = "1478--1489",
journal = "J MED CHEM",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "4",

}

RIS

TY - JOUR

T1 - Aberrant cyclization affords a C-6 modified cyclic adenosine 5'-diphosphoribose analogue with biological activity in Jurkat T cells.

AU - Moreau, Christelle

AU - Kirchberger, Tanja

AU - Zhang, Bo

AU - Thomas, Mark P

AU - Weber, Karin

AU - Guse, Andreas H.

AU - Potter, Barry V L

PY - 2012

Y1 - 2012

N2 - Two nicotinamide adenine dinucleotide (NAD(+)) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD(+) (6-N-methyl nicotinamide adenosine 5'-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5'-diphosphoribose, 11), whereas 6-thio NHD(+) (nicotinamide 6-mercaptopurine 5'-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5'-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5'-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1-cIDPR-induced Ca(2+) release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5'-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1-cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling.

AB - Two nicotinamide adenine dinucleotide (NAD(+)) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD(+) (6-N-methyl nicotinamide adenosine 5'-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5'-diphosphoribose, 11), whereas 6-thio NHD(+) (nicotinamide 6-mercaptopurine 5'-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5'-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5'-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1-cIDPR-induced Ca(2+) release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5'-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1-cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling.

KW - Animals

KW - Humans

KW - Models, Molecular

KW - Permeability

KW - Calcium/metabolism

KW - Hydrogen-Ion Concentration

KW - Jurkat Cells

KW - Structure-Activity Relationship

KW - Molecular Conformation

KW - Cyclization

KW - ADP-ribosyl Cyclase/chemistry

KW - Aplysia

KW - Cyclic ADP-Ribose/analogs & derivatives/chemical synthesis/pharmacology

KW - T-Lymphocytes/drug effects/metabolism

KW - Thioinosine/analogs & derivatives/chemical synthesis/pharmacology

KW - Animals

KW - Humans

KW - Models, Molecular

KW - Permeability

KW - Calcium/metabolism

KW - Hydrogen-Ion Concentration

KW - Jurkat Cells

KW - Structure-Activity Relationship

KW - Molecular Conformation

KW - Cyclization

KW - ADP-ribosyl Cyclase/chemistry

KW - Aplysia

KW - Cyclic ADP-Ribose/analogs & derivatives/chemical synthesis/pharmacology

KW - T-Lymphocytes/drug effects/metabolism

KW - Thioinosine/analogs & derivatives/chemical synthesis/pharmacology

M3 - SCORING: Journal article

VL - 55

SP - 1478

EP - 1489

JO - J MED CHEM

JF - J MED CHEM

SN - 0022-2623

IS - 4

M1 - 4

ER -