Sulfhydryl ligands

Hashimoto, K., Loader, J. E., and Kinsky, S. C. (1986) Iodoacetylated and biotinylated liposomes Effect of spacer length on sulfhydryl ligand binding and avidin precipitability. Bio-chim. Biophys. Acta 856, 556—565. 

Gardea-Torresdey, J.L., Tiemann, K.J., Dokken, K., and Gamez, G. 1998. Investigation of metal binding in Alfalfa biomass through chemical modification of amino and sulfhydryl ligands. Proceedings of the 1998 Conference on Hazardous Waste Research, pp. 111-21. 

The biochemical basis for the toxicity of mercury and mercury compounds results from its ability to form covalent bonds readily with sulfur. Prior to reaction with sulfur, however, the mercury must be metabolized to the divalent cation. When the sulfur is in the form of a sulfhydryl (— SH) group, divalent mercury replaces the hydrogen atom to form mercaptides, X—Hg— SR and Hg(SR)2, where X is an electronegative radical and R is protein (36). Sulfhydryl compounds are called mercaptans because of their ability to capture mercury. Even in low concentrations divalent mercury is capable of inactivating sulfhydryl enzymes and thus causes interference with cellular metaboHsm and function (31—34). Mercury also combines with other ligands of physiological importance such as phosphoryl, carboxyl, amide, and amine groups. It is unclear whether these latter interactions contribute to its toxicity (31,36). 

Fig. 10. Pharmacophores for angiotension-converting enzyme. Distances in nm. (a) The stmcture of a semirigid inhibitor and distances between essential atoms from which one pharmacophore was derived (79). (b) In another pharmacophore, atom 1 is a potential zinc ligand (sulfhydryl or carboxylate oxygen), atom 2 is a neutral hydrogen bond acceptor, atom 3 is an anion (deprotonated sulfur or charged oxygen), atom 4 indicates the direction of a hydrogen bond to atom two, and atom 5 is the central atom of a carboxylate, sulfate, or phosphate of which atom 3 is an oxygen, or atom 5 is an unsaturated carbon when atom 3 is a deprotonated sulfur. The angle 1- -2- -3- -4 is —135 to —180° or 135 to 180°, and 1- -2- -3- -5 is —90 to 90°.

There are many ligands and group-specific reagents that have been demonstrated to alter the properties of H,K-ATPase, and which are not clinically useful. For example, there is a variety of chemicals that have been used in studies on structure-function relations of H,K-ATPase and that inhibit the enzyme in vitro by modification of its amino [49,67,158], sulfhydryl [95,165,166] or carboxyl groups [140]. 

Prepare the sulfhydryl column by washing with a disulfide reducing agent. Apply 10 ml of freshly made lOmM DTT solution (15.4mg of DTT dissolved in 10ml of equilibration buffer). This treatment converts the immobilized ligands into a fully reduced form (free —SH groups). 

Several mechanisms have been postulated to account for thallium s toxicity, including ligand formation with sulfhydryl groups of enzymes and transport proteins, inhibition of cellular respiration, interaction with riboflavin and riboflavin-based cofactors, alteration of the activity of K -dependent proteins, and disruption of intracellular calcium homeostasis. ... 

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