The Experts below are selected from a list of 777 Experts worldwide ranked by ideXlab platform

Gunther Schmalzing - One of the best experts on this subject based on the ideXlab platform.

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X1 receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3,3,3-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2,2,2-(carbonylbis(imino5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were 200-fold less potent in blocking P2X1 receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X1 receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X3 receptors (Ki 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X23 P2X3 P2X1 P2X2 P2X4 P2X7. The usefulness of NF110 as a P2X3 receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks -methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X3 receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X(1) receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4',4'',4''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3',3'',3''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2',2'',2''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were >200-fold less potent in blocking P2X(1) receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X(1) receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X(3) receptors (K(i) approximately 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X(2+3) = P2X(3) > P2X(1) > P2X(2) >> P2X(4) > P2X(7). The usefulness of NF110 as a P2X(3) receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks alphabeta-methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X(3) receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.

Ralf Hausmann - One of the best experts on this subject based on the ideXlab platform.

  • The suramin analog 4,4′,4″,4‴-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF110) potently blocks P2X3 receptors: subtype selectivity is determined by location of sulfonic Acid groups. Mol Pharmacol
    2016
    Co-Authors: Ralf Hausmann, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes
    Abstract:

    We have previously identified the suramin analog 4,4,4,4-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetra-kis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X1 receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiol-ogy, three isomeric suramin analogs designated para-4,4,4,4-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF110), meta-(3,3,3,3-(carbonyl-bis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benze-nesulfonic Acid (NF448), and ortho-(2,2,2,2-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfoni

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X1 receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3,3,3-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2,2,2-(carbonylbis(imino5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were 200-fold less potent in blocking P2X1 receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X1 receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X3 receptors (Ki 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X23 P2X3 P2X1 P2X2 P2X4 P2X7. The usefulness of NF110 as a P2X3 receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks -methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X3 receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X(1) receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4',4'',4''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3',3'',3''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2',2'',2''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were >200-fold less potent in blocking P2X(1) receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X(1) receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X(3) receptors (K(i) approximately 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X(2+3) = P2X(3) > P2X(1) > P2X(2) >> P2X(4) > P2X(7). The usefulness of NF110 as a P2X(3) receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks alphabeta-methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X(3) receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.

Peter Illes - One of the best experts on this subject based on the ideXlab platform.

  • The suramin analog 4,4′,4″,4‴-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF110) potently blocks P2X3 receptors: subtype selectivity is determined by location of sulfonic Acid groups. Mol Pharmacol
    2016
    Co-Authors: Ralf Hausmann, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes
    Abstract:

    We have previously identified the suramin analog 4,4,4,4-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetra-kis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X1 receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiol-ogy, three isomeric suramin analogs designated para-4,4,4,4-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF110), meta-(3,3,3,3-(carbonyl-bis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benze-nesulfonic Acid (NF448), and ortho-(2,2,2,2-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfoni

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X1 receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3,3,3-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2,2,2-(carbonylbis(imino5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were 200-fold less potent in blocking P2X1 receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X1 receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X3 receptors (Ki 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X23 P2X3 P2X1 P2X2 P2X4 P2X7. The usefulness of NF110 as a P2X3 receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks -methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X3 receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X(1) receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4',4'',4''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3',3'',3''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2',2'',2''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were >200-fold less potent in blocking P2X(1) receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X(1) receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X(3) receptors (K(i) approximately 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X(2+3) = P2X(3) > P2X(1) > P2X(2) >> P2X(4) > P2X(7). The usefulness of NF110 as a P2X(3) receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks alphabeta-methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X(3) receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.

Zoltan Gerevich - One of the best experts on this subject based on the ideXlab platform.

  • The suramin analog 4,4′,4″,4‴-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF110) potently blocks P2X3 receptors: subtype selectivity is determined by location of sulfonic Acid groups. Mol Pharmacol
    2016
    Co-Authors: Ralf Hausmann, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes
    Abstract:

    We have previously identified the suramin analog 4,4,4,4-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetra-kis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X1 receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiol-ogy, three isomeric suramin analogs designated para-4,4,4,4-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF110), meta-(3,3,3,3-(carbonyl-bis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benze-nesulfonic Acid (NF448), and ortho-(2,2,2,2-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfoni

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X1 receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3,3,3-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2,2,2-(carbonylbis(imino5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were 200-fold less potent in blocking P2X1 receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X1 receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X3 receptors (Ki 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X23 P2X3 P2X1 P2X2 P2X4 P2X7. The usefulness of NF110 as a P2X3 receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks -methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X3 receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X(1) receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4',4'',4''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3',3'',3''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2',2'',2''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were >200-fold less potent in blocking P2X(1) receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X(1) receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X(3) receptors (K(i) approximately 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X(2+3) = P2X(3) > P2X(1) > P2X(2) >> P2X(4) > P2X(7). The usefulness of NF110 as a P2X(3) receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks alphabeta-methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X(3) receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.

Sabine Meis - One of the best experts on this subject based on the ideXlab platform.

  • The suramin analog 4,4′,4″,4‴-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF110) potently blocks P2X3 receptors: subtype selectivity is determined by location of sulfonic Acid groups. Mol Pharmacol
    2016
    Co-Authors: Ralf Hausmann, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes
    Abstract:

    We have previously identified the suramin analog 4,4,4,4-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetra-kis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X1 receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiol-ogy, three isomeric suramin analogs designated para-4,4,4,4-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF110), meta-(3,3,3,3-(carbonyl-bis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benze-nesulfonic Acid (NF448), and ortho-(2,2,2,2-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfoni

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X1 receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4,4,4(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3,3,3-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2,2,2-(carbonylbis(imino5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were 200-fold less potent in blocking P2X1 receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X1 receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X3 receptors (Ki 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X23 P2X3 P2X1 P2X2 P2X4 P2X7. The usefulness of NF110 as a P2X3 receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks -methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X3 receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.

  • the suramin analog 4 4 4 4 carbonylbis imino 5 1 3 benzenetriylbis carbonylimino tetra kis Benzenesulfonic Acid nf110 potently blocks p2x3 receptors subtype selectivity is determined by location of sulfonic Acid groups
    Molecular Pharmacology, 2006
    Co-Authors: Ralf Hausmann, Jurgen Rettinger, Zoltan Gerevich, Sabine Meis, Matthias U Kassack, Peter Illes, Gunter Lambrecht, Gunther Schmalzing
    Abstract:

    We have previously identified the suramin analog 4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic Acid (NF449) as a low nanomolar potency antagonist of recombinant P2X(1) receptors. Here, we characterize, by two-electrode voltage-clamp electrophysiology, three isomeric suramin analogs designated para-4,4',4'',4''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetrakis-Benzenesulfonic Acid (NF110), meta-(3,3',3'',3''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (NF448), and ortho-(2,2',2'',2''''-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-Benzenesulfonic Acid (MK3) with respect to their potency in antagonizing rat P2X receptor-mediated inward currents in Xenopus laevis oocytes. Meta, para, and ortho refer to the position of the single sulfonic Acid group relative to the amide bond linking the four symmetrically oriented Benzenesulfonic Acid moieties to the central, invariant suramin core. NF448, NF110, and MK3 were >200-fold less potent in blocking P2X(1) receptors than NF449, from which they differ structurally only by having one instead of two sulfonic Acid residues per benzene ring. Although the meta- and ortho-isomers retained P2X(1) receptor selectivity, the para-isomer NF110 exhibited a significantly increased activity at P2X(3) receptors (K(i) approximately 36 nM) and displayed the following unique selectivity profile among suramin derivatives: P2X(2+3) = P2X(3) > P2X(1) > P2X(2) >> P2X(4) > P2X(7). The usefulness of NF110 as a P2X(3) receptor antagonist in native tissues could be demonstrated by showing that NF110 blocks alphabeta-methylene-ATP-induced currents in rat dorsal root ganglia neurons with similar potency as recombinant rat P2X(3) receptors. Together, these data highlight the importance of both the number and exact location of negatively charged groups for P2X subtype potency and selectivity.