Disease relevance of Pyridine disulfide analog

• To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4(+) T cells in human lymphoid tissues ex vivo [1].
• We used the compound 2,2'-dithiodipyridine (aldrithiol-2; AT-2) to covalently modify the essential zinc fingers in the nucleocapsid (NC) protein of human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) virions, thereby inactivating infectivity [2].
• Here we report that HIV-1 infection induced apoptosis primarily in productively infected thymocytes; aldrithiol-2 or Efavirenz treatment largely abrogated HIV-1-induced apoptosis [3].
• We used chemically inactivated aldrithiol-2 (AT-2) simian immunodeficiency virus (SIV) with functional envelope glycoproteins to study virus interactions with DCs and developed an in vitro system to evaluate the quality of SIV antigen (Ag) presentation by DCs to T cells [4].
• Treatment with Aldrithiol-2 resulted in extensive reaction with the nucleocapsid protein of treated virus, as shown by immunoblot and high-performance liquid chromatography (HPLC) analysis [5].

High impact information on Pyridine disulfide analog

• This activation was independent of viral gene expression, because it occurred after treatment of MMTV with ultraviolet light or 2,2'-dithiodipyridine and in azidothymidine-treated mice [6].
• Within 10 minutes of exposure to 2,2'-dithiodipyridine (DTDP, a specific lipophilic oxidizer of sulfhydryl groups), Ca2+ current was reduced compared with the control value, with no significant change in the kinetics and no shift in the current-voltage relations [7].
• With MT overexpression, we observed an acute buffering effect manifested as a dampening of stimulus-induced increases in [Zn2+]i. In contrast, we also saw enhanced zinc release with application of the sulfhydryl oxidizing agent 2,2'-dithiodipyridine [8].
• The membrane-permeant oxidizing agent 2,2'-dithiodipyridine (DTDP) can induce Zn(2+) release from metalloproteins in cell-free systems [9].
• Thiol oxidation by 2,2'-dithiodipyridine causes a reversible increase in cytoplasmic free Ca2+ concentration in pancreatic beta-cells. Role for inositol 1,4,5-trisphosphate-sensitive Ca2+ stores [10].

Biological context of Pyridine disulfide analog

• The rate of reaction of ALDH with 2,2'-dithiodipyridine is only slightly reduced by DES, suggesting that the site at which thiol modifiers react and the DES binding site are different [11].

Anatomical context of Pyridine disulfide analog

• 2,2'-Dithiodipyridine (2,2'-DTDP), a reactive disulphide that mobilizes Ca2+ from ryanodine-sensitive Ca2+ stores in muscle, induced a biphasic increase in cytoplasmic free Ca2+ concentration ([Ca2+]i) in pancreatic beta-cells loaded with fura 2 [10].
• Human lymphoid cell cultures were treated with 2,2'-dithiodipyridine, a thiol reacting agent which produces SS bridges inside the living cells [12].
• In 2001, we showed in vitro that dendritic cells (DCs) of HIV-infected patients loaded with autologous HIV chemically inactivated by aldrithiol-2 were capable of raising an HIV-specific cellular immune response powerful enough to allow the destruction of autologous HIV- infected CD4 T cells [13].

Associations of Pyridine disulfide analog with other chemical compounds

• The reaction of the active-site thiol group of papain with 5,5'-dithiobis-(2-nitrobenzoic acid) at pH 8 and 2,2'-dithiobispyridine at pH 4 was blocked by complex-formation [14].
• The binding of diethylstilbestrol (DES) to aldehyde dehydrogenase (ALDH) has a very similar effect on the dehydrogenase activity of the enzyme as has modification of the enzyme by 2,2'-dithiodipyridine [Kitson, T.M. (1982) Biochem. J. 207, 81-89] [11].
• The reactions of hemerythrin from Phascolopsis gouldii with the specific sulfhydryl reagents 5,5'-dithiobis(2-nitrobenzoate), 2,2'-dithiodipyridine, and 4,4'-dithiodipyridine were studied at 25 degrees C. Spectrophotometric measurements showed that 1 mol of disulfide reacted per protein subunit consistent with a single cysteine at residue 50 [15].
• It was also shown that sulphydryl reagents, N-ethylmaleimide and 2,2'-dithiodipyridine, induced similar fluorescence changes [16].

Gene context of Pyridine disulfide analog

• Titration of one of the 10 SH groups of native cathepsin B with 2,2'-dithiodipyridine resulted in complete loss of enzyme activity [17].
• With transient (stop-flow) kinetics, DTNB [5,5'-dithiobis-(2-nitrobenzoic acid)] and 2,2'-dithiodipyridine progress curves cannot be fitted by the sum of exponential terms based only on classes of cysteines [18].
• The activation of aldehyde dehydrogenase by diethylstilboestrol and 2,2'-dithiodipyridine [19].
• Three amine oxides, two aliphatic and one aromatic, and 2,2'-dithiodipyridine were found to be weak reversible inhibitors of acetylcholinesterase [20].
• The chemical modification of thymidylate synthase with 2,2'-dithiodipyridine was shown to be specific for the catalytic sulfhydryl groups of the native dimer, titrating 1.51 sulfhydryl groups, while 2.93 cysteines were modified in the GnHCl-denatured protein [21].

Analytical, diagnostic and therapeutic context of Pyridine disulfide analog

• To establish the usefulness of this matrix for immobilization and the conditions required for chromatography, model studies were conducted with 2,2'-dithiodipyridine [21].

References