Studies on suramin. 8. The action of the drug on enzymes and some other proteins. General considerations

Town, Bernard William; Wills, Eric D.; Wilson, Erica J.; Wormall, A.

doi:10.1042/bj0470149

Cited by 42 publications

(7 citation statements)

References 9 publications

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“…Previous extensive studies have shown that suramin (compound I) binds to plasma proteins and inhibits certain enzymes, probably by interaction of the sulphonic acid groups with the basic groups of the protein (Spinks, 1948;Wilson & Wormall, 1949;Town, Wills, Wilson & Wormall, 1950;. Such a mechanism may well explain the inhibition of a-toxin, especially by compounds of group 1, although the results of the present study suggest that the sulphonic acid groups alone do not govern the degree of inhibition.…”

Section: Resultscontrasting

confidence: 61%

Inhibition of staphylococcal α-toxin. A kinetic evaluation of aromatic polysulphonic acids as inhibitors of haemolysis

Wright

Arbuthnott

Lominski

1968

Biochemical Journal

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1. The effect of a number of aromatic polysulphonic acids on the kinetics of haemolysis of rabbit erythrocyte suspensions by crude staphylococcal alpha-toxin was studied at pH8.6 and 6.8. 2. All of the inhibitory compounds caused an increase in the prelytic lag time (tau) of the sigmoid haemolysis curves, an increase in the time to reach 50% haemolysis (t((1/2))) and a decrease in the maximum rate of haemolysis (R(max.)). The most inhibitory compounds caused a 50% decrease in R(max.) at concentrations between 0.1 and 0.2mm. 3. The effect of pH varied considerably: compounds (I) and (II) were almost equally inhibitory at both pH values, compounds (IV) and (IX) were more inhibitory at pH6.8 than at pH8.6, and compounds (VII), (VIII), (X), (XI) and (XII) were more inhibitory at pH8.6. 4. Increased time of premixing alpha-toxin with compound (I) caused increased inhibition. 5. An attempt was made, where possible, to relate the inhibitory activity to the structure of the test compound.

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Section: Resultscontrasting

confidence: 61%

Inhibition of staphylococcal α-toxin. A kinetic evaluation of aromatic polysulphonic acids as inhibitors of haemolysis

Wright

Arbuthnott

Lominski

1968

Biochemical Journal

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“…In the case of suramin, it was found that the drug binds with no domain-specific interactions and with no selectivity, and thus the protein-suramin interaction is non-specific [11]. It has been known for some time that suramin will bind with high affinity to serum albumin [12]. Preincubation of HIV-1 RT with template/primer, dNTP or a combination of the two will not protect the enzyme from inactivation by (-)epicatechin 3-gallate (results not shown), further suggesting that the interaction is non-specific.…”

Section: Discussionmentioning

confidence: 99%

Observations on the inhibition of HIV-1 reverse transcriptase by catechins

Moore

Pìzza

1992

Biochemical Journal

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The sensitivity and specificity of the inhibition of HIV-1 reverse transcriptase by various catechins have been examined. As previously reported, (-)epicatechin 3-gallate inhibits the viral polymerase. However, it is noted here that this inhibition is not observed in the presence of either serum albumin or Triton X-100. Other catechins behave similarly to (-)epicatechin 3-gallate in that they inhibit polymerase activity only in the absence of these reagents. Additionally, other DNA polymerases are inhibited to a similar degree by (-)epicatechin 3-gallate. Taken cumulatively, these results suggest that these catechins, and in particular (-)epicatechin 3-gallate, bind with no apparent selectivity and that the observed inhibition of HIV-1 reverse transcriptase is non-specific in nature.

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“…Several suramin analogs have been developed subsequently with the aim of improving selectivity for P2X 1 receptors, because blockers of P2X 1 receptors on platelets hold promise as antithrombotic agents (15,16). One of these is 4,4Ј,4Љ,4ٞ-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid (NF449), 2 which blocks P2X 1 receptors in low nanomolar concentrations and has good selectivity over P2X 3 receptors (17,18).…”

Section: Suramin (8-[(4-methyl-3-{[3-({[3-({2-methyl-5-[(468-trisulmentioning

confidence: 99%

Ectodomain Lysines and Suramin Block of P2X1 Receptors

Sim

Broomhead

North

2008

Journal of Biological Chemistry

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P2X 1 receptors belong to a family of cation channels gated by extracellular ATP; they are found inter alia in smooth muscle, platelets, and immune cells. Suramin has been widely used as an antagonist at P2X receptors, and its analog 4,4,4؆,4ٟ-[carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino))] tetrakis-benzene-1,3-disulfonic acid (NF449) is selective for the P2X 1 subtype. Human and mouse P2X 1 receptors were expressed in human embryonic kidney cells, and membrane currents evoked by ATP were recorded. ATP (10 nM to 100 M) was applied only once to each cell, to avoid the profound desensitization exhibited by P2X 1 receptors. Suramin (10 M) and NF449 (3-300 nM) effectively blocked the human receptor. Suramin had little effect on the mouse receptor. Suramin and NF449 are polysulfonates, with six and eight negative charges, respectively. We hypothesized that species differences might result from differences in positive residues presented by the large receptor ectodomain. Four lysines in the human sequence (Lys 111 , Lys 127 , Lys 138 , and Lys 148 ) were changed individually and together to their counterparts in the mouse sequence. The substitution K138E, either alone or together with K111Q, K127Q, and K148N, reduced the sensitivity to block by both suramin and NF449. Conversely, when lysine was introduced into the mouse receptor, the sensitivity to block by suramin and NF449 was much increased for E138K, but not for Q111K, Q127K, or N148K. The results explain the marked species difference in antagonist sensitivity and identify an ectodomain lysine residue that plays a key role in the binding of both suramin and NF449 to P2X 1 receptors.

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Studies on suramin. 8. The action of the drug on enzymes and some other proteins. General considerations

Cited by 42 publications

References 9 publications

Inhibition of staphylococcal α-toxin. A kinetic evaluation of aromatic polysulphonic acids as inhibitors of haemolysis

Inhibition of staphylococcal α-toxin. A kinetic evaluation of aromatic polysulphonic acids as inhibitors of haemolysis

Observations on the inhibition of HIV-1 reverse transcriptase by catechins

Ectodomain Lysines and Suramin Block of P2X1 Receptors

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