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Selenium versus sulfur: Reversibility of chemical reactions and resistance to permanent oxidation in proteins and nucleic acids.

ABSTRACT: This review highlights the contributions of Jean Chaudière to the field of selenium biochemistry. Chaudière was the first to recognize that one of the main reasons that selenium in the form of selenocysteine is used in proteins is due to the fact that it strongly resists permanent oxidation. The foundations for this important concept was laid down by Al Tappel in the 1960's and even before by others. The concept of oxygen tolerance first recognized in the study of glutathione peroxidase was further advanced and refined by those studying [NiFeSe]-hydrogenases, selenosubtilisin, and thioredoxin reductase. After 200 years of selenium research, work by Marcus Conrad and coworkers studying glutathione peroxidase-4 has provided definitive evidence for Chaudière's original hypothesis (Ingold et al., 2018) [36]. While the reaction of selenium with oxygen is readily reversible, there are many other examples of this phenomenon of reversibility. Many reactions of selenium can be described as "easy in - easy out". This is due to the strong nucleophilic character of selenium to attack electrophiles, but then this reaction can be reversed due to the strong electrophilic character of selenium and the weakness of the selenium-carbon bond. Several examples of this are described.

SUBMITTER: Maroney MJ

PROVIDER: S-EPMC6158117 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Selenium versus sulfur: Reversibility of chemical reactions and resistance to permanent oxidation in proteins and nucleic acids.

Maroney Michael J MJ Hondal Robert J RJ

Free radical biology & medicine 20180326

This review highlights the contributions of Jean Chaudière to the field of selenium biochemistry. Chaudière was the first to recognize that one of the main reasons that selenium in the form of selenocysteine is used in proteins is due to the fact that it strongly resists permanent oxidation. The foundations for this important concept was laid down by Al Tappel in the 1960's and even before by others. The concept of oxygen tolerance first recognized in the study of glutathione peroxidase was furt ...[more]

PMID: 29588180

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Project description:A critical source of insight into biological function is derived from the chemist's ability to create new covalent bonds between molecules, whether they are endogenous or exogenous to a biological system. A daunting impediment to selective bond formation, however, is the myriad of reactive functionalities present in biological milieu. The high reactivity of the most abundant molecule in biology, water, makes the challenges all the more difficult. We have met these challenges by exploiting the reactivity of sulfur and selenium in acyl transfer reactions. The reactivity of both sulfur and selenium is high compared with that of their chalcogen congener, oxygen. In this Account, we highlight recent developments in this arena, emphasizing contributions from our laboratory. One focus of our research is furthering the chemistry of native chemical ligation (NCL) and expressed protein ligation (EPL), two related processes that enable the synthesis and semisynthesis of proteins. These techniques exploit the lower pK(a) of thiols and selenols relative to alcohols. Although a deprotonated hydroxyl group in the side chain of a serine residue is exceedingly rare in a biological context, the pK(a) values of the thiol in cysteine (8.5) and of the selenol in selenocysteine (5.7) often render these side chains anionic under physiological conditions. NCL and EPL take advantage of the high nucleophilicity of the thiolate as well as its utility as a leaving group, and we have expanded the scope of these methods to include selenocysteine. Although the genetic code limits the components of natural proteins to 20 or so α-amino acids, NCL and EPL enable the semisynthetic incorporation of a limitless variety of nonnatural modules into proteins. These modules are enabling chemical biologists to interrogate protein structure and function with unprecedented precision. We are also pursuing the further development of the traceless Staudinger ligation, through which a phosphinothioester and azide form an amide. We first reported this chemical ligation method, which leaves no residual atoms in the product, in 2000. Our progress in effecting the reaction in water, without an organic cosolvent, was an important step in the expansion of its utility. Moreover, we have developed the traceless Staudinger reaction as a means for immobilizing proteins on a solid support, providing a general method of fabricating microarrays that display proteins in a uniform orientation. Along with NCL and EPL, the traceless Staudinger ligation has made proteins more readily accessible targets for chemical synthesis and semisynthesis. The underlying acyl transfer reactions with sulfur and selenium provide an efficient means to synthesize, remodel, and immobilize proteins, and they have enabled us to interrogate biological systems.

Project description:In this paper, digital quantitative detection of nucleic acids was achieved at the single-molecule level by chemical initiation of over one thousand sequence-specific, nanoliter isothermal amplification reactions in parallel. Digital polymerase chain reaction (digital PCR), a method used for quantification of nucleic acids, counts the presence or absence of amplification of individual molecules. However, it still requires temperature cycling, which is undesirable under resource-limited conditions. This makes isothermal methods for nucleic acid amplification, such as recombinase polymerase amplification (RPA), more attractive. A microfluidic digital RPA SlipChip is described here for simultaneous initiation of over one thousand nL-scale RPA reactions by adding a chemical initiator to each reaction compartment with a simple slipping step after instrument-free pipet loading. Two designs of the SlipChip, two-step slipping and one-step slipping, were validated using digital RPA. By using the digital RPA SlipChip, false-positive results from preinitiation of the RPA amplification reaction before incubation were eliminated. End point fluorescence readout was used for "yes or no" digital quantification. The performance of digital RPA in a SlipChip was validated by amplifying and counting single molecules of the target nucleic acid, methicillin-resistant Staphylococcus aureus (MRSA) genomic DNA. The digital RPA on SlipChip was also tolerant to fluctuations of the incubation temperature (37-42 °C), and its performance was comparable to digital PCR on the same SlipChip design. The digital RPA SlipChip provides a simple method to quantify nucleic acids without requiring thermal cycling or kinetic measurements, with potential applications in diagnostics and environmental monitoring under resource-limited settings. The ability to initiate thousands of chemical reactions in parallel on the nanoliter scale using solvent-resistant glass devices is likely to be useful for a broader range of applications.

Dataset Information

Selenium versus sulfur: Reversibility of chemical reactions and resistance to permanent oxidation in proteins and nucleic acids.

Publications

Selenium versus sulfur: Reversibility of chemical reactions and resistance to permanent oxidation in proteins and nucleic acids.

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