1-Methylpyridinium-4-(4-phenylmethanethiosulfonate) iodide, MTS-MPP+, a novel scanning cysteine accessibility method (SCAM) reagent for monoamine transporter studies

Gallardo-Godoy, Alejandra; Torres-Altoro, Melissa I.; White, Kellie J.; Barker, Eric L.; Nichols, David E.

doi:10.1016/j.bmc.2006.09.058

Cited by 23 publications

(23 citation statements)

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“…The results were confirmed by additional SCAM studies using MTS‐MPP + , a novel monoamine transporter SCAM reagent shown to be more potent at SERT than MTSET (Gallardo‐Godoy et al 2007). These results support a model where F556C/hSERT is exposed to the hydrophilic environment of the permeation pathway and may suggest that F556C/hSERT is localized close to the substrate binding site or in a conformationally sensitive site that makes F556C/hSERT accessible to MTS reagents near the entrance to the substrate permeation pathway.…”

Section: Discussionmentioning

confidence: 72%

“…To confirm and validate our experiments, additional SCAM studies were performed using MTS-MPP + , a novel monoamine transporter methanethiosulfonate reagent proven to be more potent at SERT than MTSET (Gallardo-Godoy et al 2007). Consistent with the results above, F556C/hSERT was the only mutant that showed a Cells were plated and transfected as described in Materials and Methods.…”

Section: Substitution Of Phenylalanine At Position 556 With Serine Rementioning

confidence: 64%

“…Cysteine mutants were generated to explore further the possibility that these residues are localized in the pore‐forming region in hSERT. F556C/hSERT was accessible to [2‐(trimethylammonium)ethyl]methanethiosulfonate bromide (MTSET) and the novel MTS reagent 4‐(1‐methylpyridinium)phenylmethanethiosulfonate iodide (MTS‐MPP + ) (Gallardo‐Godoy et al 2007) and upon reaction, reduced transport of the substrate. Furthermore, MTSET inhibited current induced by 5‐HT and MPP + at F556C/hSERT, suggesting that this residue is located in the hydrophilic environment of the protein.…”

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confidence: 99%

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Helix XI contributes to the entrance of the serotonin transporter permeation pathway

et al. 2008

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The sodium-dependent transporters for dopamine, norepinephrine, and serotonin that regulate neurotransmission, also translocate the neurotoxin 1-methyl-4-phenylpyridinium (MPP + ). Previous studies implicated residues in transmembrane helix (TMH) XI of DAT as important sites for MPP + transport. We examined the importance of TMH XI residues F551 and F556 for MPP + translocation by human SERT. Mutations at hSERT F556, but not F551, reduced both 5-HT and MPP + transport compared to wild type. However, F556S/hSERT showed a reduction in surface expression explaining the decrease of transport activity for 5-HT, but did not account for the decrease in MPP + transport observed. Cysteine mutants at those positions confirmed the accessibility of hSERT/F556 to different methanethiosulfonate (MTS) reagents, suggesting its presence in a hydrophilic environment of the protein. In the presence of MTSET, current induced by 5-HT and MPP + was inhibited at the F556C mutant. In agreement with our homology model of SERT, based on the leucine transporter (LeuT Aa ) from Aquifex aeolicus structure, these results are consistent with the hypothesis that a portion of TMH XI lines the entrance into the substrate permeation pathway.Keywords: cocaine; antidepressant; amphetamine; biogenic amine; neurotoxinThe neurotoxin 1-methyl-4-phenylpyridinium (MPP + ) is translocated by the neurotransmitter transporters for dopamine, norepinephrine, and serotonin (DAT, NET, and SERT, respectively) (Javitch et al. 1985;Paczkowski et al. 1999;Sitte et al. 2000Sitte et al. , 2001Martel and Keating 2003). These transporters belong to the Na + /Cl À -dependent family of transporters that contain 12 transmembrane helices (TMHs) with intracellular N and C termini. Previous studies of DAT identified residues important for MPP + translocation in TMHs I, VII, and XI (Kitayama et al. 1992(Kitayama et al. , 1993Mitsuhata et al. 1998). Simultaneous mutation of TMH XI residues S527, Y533, and S538 to alanine in rat DAT (rDAT) resulted in enhanced MPP + uptake compared to wild-type rDAT (Kitayama et al. 1993). These mutations exerted modest effects on dopamine uptake but had little impact on cocaine analog affinity (Kitayama et al. 1993). Although that study suggests determinants in TMH XI of rDAT important for MPP + transport, the specific role of these residues in DAT function remains unclear. Subsequent mutation of rDAT/ Y533 to phenylalanine, the corresponding residue in human DAT (hDAT), increased the velocity of MPP + uptake, suggesting that F533 in hDAT was important for MPP + uptake (Mitsuhata et al. 1998). Using the available mutation data from DAT, Ravna and Edvardsen (2001)

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Section: Discussionmentioning

confidence: 72%

Section: Substitution Of Phenylalanine At Position 556 With Serine Rementioning

confidence: 64%

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confidence: 99%

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Helix XI contributes to the entrance of the serotonin transporter permeation pathway

et al. 2008

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“…Ligand synthesis: 4-( pyridin-4′-yl)benzenethiol was synthesized according to the literature 49,50 with minor modifications. A detailed protocol is available in the ESI.…”

Section: Materials and Chemicalsmentioning

confidence: 99%

Controlled assembly and single electron charging of monolayer protected Au₁₄₄ clusters: an electrochemistry and scanning tunneling spectroscopy study

Bodappa¹,

Fluch²,

Fu³

et al. 2014

Nanoscale

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Single gold particles may serve as room temperature single electron memory units because of their size dependent electronic level spacing. Here, we present a proof-of-concept study by electrochemically controlled scanning probe experiments performed on tailor-made Au particles of narrow dispersity. In particular, the charge transport characteristics through chemically synthesized hexane-1-thiol and 4-pyridylbenzene-1-thiol mixed monolayer protected Au(144) clusters (MPCs) by differential pulse voltammetry (DPV) and electrochemical scanning tunneling spectroscopy (EC-STS) are reported. The pyridyl groups exposed by the Au-MPCs enable their immobilization on Pt(111) substrates. By varying the humidity during their deposition, samples coated by stacks of compact monolayers of Au-MPCs or decorated with individual, laterally separated Au-MPCs are obtained. DPV experiments with stacked monolayers of Au(144)-MPCs and EC-STS experiments with laterally separated individual Au(144)-MPCs are performed both in aqueous and ionic liquid electrolytes. Lower capacitance values were observed for individual clusters compared to ensemble clusters. This trend remains the same irrespective of the composition of the electrolyte surrounding the Au(144)-MPC. However, the resolution of the energy level spacing of the single clusters is strongly affected by the proximity of neighboring particles.

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“…Thiosulfonates are structural motifs in the antibacterial agent allicin [50] . Thiosulfonates exhibit also biological properties such as antifungal, antimicrobial [51,52] and anticancer activities, [53] and also used as cysteine scanning reagents [54,55] . Recently, thiosulfonates have been used as synthetic precursors to incorporate sulfones and thioethers into organic molecules [56] …”

Section: Electrochemical Synthesis Of Thiosulfonatesmentioning

confidence: 99%

Recent Advances in the Electrochemical Synthesis of Organosulfur Compounds

Amri

Wirth

2021

The Chemical Record

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Organosulfur compounds are being widely used in medicinal chemistry, as well as in organic transformations and in synthetic applications. Because of their interest in many areas, the development of sustainable and green synthetic methods to access various organosulfur compounds has a high influence on the chemistry community. Electroorganic synthesis has become a very valuable methodology for the synthesis of organosulfur compounds during the last decade. The use of electrochemical technology offers a green, sustainable and safe alternative to prepare and modify such compounds. This review summarises recent developments in the preparation of organosulfur compounds such as sulfoxides, sulfones, sulfinic esters, sulfonamides, thiosulfonates, sulfonyl fluorides and sulfoximines under electrochemical reaction conditions.

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1-Methylpyridinium-4-(4-phenylmethanethiosulfonate) iodide, MTS-MPP+, a novel scanning cysteine accessibility method (SCAM) reagent for monoamine transporter studies

Cited by 23 publications

References 19 publications

Helix XI contributes to the entrance of the serotonin transporter permeation pathway

Helix XI contributes to the entrance of the serotonin transporter permeation pathway

Controlled assembly and single electron charging of monolayer protected Au₁₄₄ clusters: an electrochemistry and scanning tunneling spectroscopy study

Recent Advances in the Electrochemical Synthesis of Organosulfur Compounds

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1-Methylpyridinium-4-(4-phenylmethanethiosulfonate) iodide, MTS-MPP+, a novel scanning cysteine accessibility method (SCAM) reagent for monoamine transporter studies

Cited by 23 publications

References 19 publications

Helix XI contributes to the entrance of the serotonin transporter permeation pathway

Helix XI contributes to the entrance of the serotonin transporter permeation pathway

Controlled assembly and single electron charging of monolayer protected Au144 clusters: an electrochemistry and scanning tunneling spectroscopy study

Recent Advances in the Electrochemical Synthesis of Organosulfur Compounds

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Controlled assembly and single electron charging of monolayer protected Au₁₄₄ clusters: an electrochemistry and scanning tunneling spectroscopy study