Close correlation between thiolate basicity and certain NMR parameters in cysteine and cystine microspecies

Juliana Ferreira de Santana; Arash Mirzahosseini; Beáta Mándity; Dóra Bogdán; István Mándity; Béla Noszál

doi:10.1371/journal.pone.0264866

Close correlation between thiolate basicity and certain NMR parameters in cysteine and cystine microspecies

PLoS One. 2022 Mar 11;17(3):e0264866. doi: 10.1371/journal.pone.0264866. eCollection 2022.

Authors

Juliana Ferreira de Santana¹, Arash Mirzahosseini^{1

2}, Beáta Mándity³, Dóra Bogdán^{3

4}, István Mándity^{3

4}, Béla Noszál^{1

2}

Affiliations

¹ Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary.
² Research Group of Drugs of Abuse and Doping Agents, Hungarian Academy of Sciences, Budapest, Hungary.
³ MTA TTK Lendület Artificial Transporter Research Group, Institute of Materials and Environmental Chemistry, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
⁴ Department of Organic Chemistry, Semmelweis University, Budapest, Hungary.

Abstract

The imbalance between prooxidants and antioxidants in biological systems, known as oxidative stress, can lead to a disruption of redox signaling by the reactive oxygen/nitrogen species and is related to severe diseases. The most vulnerable moiety targeted by oxidant species in the redox signaling pathways is the thiol (SH) group in the cysteine residues, especially in its deprotonated (S-) form. Cysteine, along with its oxidized, disulfide-containing form, cystine, constitute one of the most abundant low molecular weight biological redox couples, providing a significant contribution to the redox homeostasis in living systems. In this work, NMR spectra from cysteine, cystine, and cysteine-containing small peptides were thoroughly studied at the submolecular level, and through the chemical shift data set of their certain atoms it is possible to estimate either thiolate basicity or the also related standard redox potential. Regression analysis demonstrated a strong linear relationship for chemical shift vs thiolate logK of the cysteine microspecies data. The αCH 13C chemical shift is the most promising estimator of the acid-base and redox character.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cysteine* / chemistry
Cystine* / metabolism
Glutathione / metabolism
Oxidation-Reduction
Reactive Nitrogen Species
Reactive Oxygen Species / metabolism
Sulfhydryl Compounds / metabolism

Substances

Reactive Nitrogen Species
Reactive Oxygen Species
Sulfhydryl Compounds
Cystine
Glutathione
Cysteine

Grants and funding

The research was financed by the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the molecular biology thematic programme of the Semmelweis University, and the ÚNKP-21-5-SE-4 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. The Lendület grant from the Hungarian Academy of Sciences is gratefully acknowledged. This work was completed in the ELTE Thematic Excellence Programme supported by the Hungarian Ministry for Innovation and Technology. Project no. 2018-1.2.1-NKP-2018-00005 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the 2018-1.2.1-NKP funding scheme. Juliana Ferreira de Santana is grateful for the Stipendium Hungaricum Scholarship. Arash Mirzahosseini is grateful for the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.