Deoxyribonucleoside 3‘-<i>O</i>-(2-Thio- and 2-Oxo-“spiro”-4,4-pentamethylene-1,3,2-oxathiaphospholane)s:  Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides

Stec, Wojciech J.; Karwowski, Bolesław T.; Boczkowska, Małgorzata; Guga, Piotr; Koziołkiewicz, Maria; Sochacki, Marek; Wieczorek, and Michał W.; Błaszczyk, Jarosław

doi:10.1021/ja973801j

Cited by 117 publications

(124 citation statements)

References 48 publications

(73 reference statements)

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“…Using the dicyanoethyl diselenide reagent [90], the Se-atom was protected by a 2-cyanoethyl group, which prevents the Se oxidation in the early stage. In addition, similar to the stereochemically defined phosphorothioate oligonucleotide synthesis [91], Stec and co-workers [92] have also developed an oxathiaphospholane-based novel approach to control the configuration at the P-centers. As shown in Scheme 9, the diastereoisomerically pure seleno-oxathiaphospholane monomer intermediate 8 was synthesized and separated in satisfactory yield.…”

Section: 22mentioning

confidence: 99%

Selenium Derivatization of Nucleic Acids for X‐Ray Crystal‐Structure and Function Studies

Sheng

Huang

2010

Chemistry & Biodiversity

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It is estimated that over two thirds of all new crystal structures of proteins are determined via the protein selenium derivatization (selenomethionine (Se-Met) strategy). This selenium derivatization strategy via MAD (multi-wavelength anomalous dispersion) phasing has revolutionized protein X-ray crystallography. Through our pioneer research, similarly, Se has also been successfully incorporated into nucleic acids to facilitate the X-ray crystal-structure and function studies of nucleic acids. Currently, Se has been stably introduced into nucleic acids by replacing nucleotide O-atom at the positions 2', 4', 5', and in nucleobases and non-bridging phosphates. The Se derivatization of nucleic acids can be achieved through solid-phase chemical synthesis and enzymatic methods, and the Se-derivatized nucleic acids (SeNA) can be easily purified by HPLC, FPLC, and gel electrophoresis to obtain high purity. It has also been demonstrated that the Se derivatization of nucleic acids facilitates the phase determination via MAD phasing without significant perturbation. A growing number of structures of DNAs, RNAs, and protein-nucleic acid complexes have been determined by the Se derivatization and MAD phasing. Furthermore, it was observed that the Se derivatization can facilitate crystallization, especially when it is introduced to the 2'-position. In addition, this novel derivatization strategy has many advantages over the conventional halogen derivatization, such as more choices of the modification sites via the atom-specific substitution of the nucleotide O-atom, better stability under X-ray radiation, and structure isomorphism. Therefore, our Se-derivatization strategy has great potentials to provide rational solutions for both phase determination and high-quality crystal growth in nucleic-acid crystallography. Moreover, the Se derivatization generates the nucleic acids with many new properties and creates a new paradigm of nucleic acids. This review summarizes the recent developments of the atomic site-specific Se derivatization of nucleic acids for structure determination and function study. Several applications of this Se-derivatization strategy in nucleic acid and protein research are also described in this review.

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Section: 22mentioning

confidence: 99%

Selenium Derivatization of Nucleic Acids for X‐Ray Crystal‐Structure and Function Studies

Sheng

Huang

2010

Chemistry & Biodiversity

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“…37 This is unacceptably low efficiency, compared to 92-94% repetitive yield noted for OTP monomers of DNA 11 and LNA 12 series. To acquire an insight into a possible mechanism contributing to the problem, a PS-GNA oligonucleotide ( G U PS ) 11 dA has been synthesized using a modied 28 phosphoramidite/sulfurization methodology and the sarcosine linker. A 2-cyanoethyl-N,N-diisopropylphosphoramidite derivative of DMT-G U was used (prepared according to ref.…”

Section: Attempts At Solid Phase Synthesis Of P-stereodened Ps-gna Omentioning

confidence: 98%

P-Stereodefined phosphorothioate analogs of glycol nucleic acids—synthesis and structural properties

et al. 2018

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Enantiomerically pure, protected acyclic nucleosides of the GNA type (glycol nucleic acids) ( G N 0 ), obtained from (R)-(+)-and (S)-(À)-glycidols and the four canonical DNA nucleobases (Ade, Cyt, Gua and Thy), were transformed into 3 0 -O-DMT-protected 2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane derivatives (OTP-G N 0 ) containing a second stereogenic center at the phosphorus atom. These monomers were chromatographically separated into P-diastereoisomers, which were further used for the synthesis of P-stereodefined "dinucleoside"

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“…Table 1 contains collection of interatomic distances, which involve S or Se atoms, and shows that the distances which involve Se atoms are much longer from the distances which involve S atoms. All examples, which are provided in Table 1, have been selected from author's previous work on X-ray structure determination of small-molecular organic compounds such as phosphoroorganic disulfides and diselenides [35][36][37][38][39][40][41], selenides [42], dithianes, dithiolanes, oxathiaphospholanes, dithiaphospholanes and oxaselenaphospholanes [43][44][45][46][47][48][49][50][51][52][53], phosphoramidothioates [44], phosphoramidoselenoates [54], sulfoxides [55][56][57][58][59] and thiophosphoryl compounds [60]. For full listing of compounds 1-42 included in that comparison, please see supplementary material.…”

Section: Introductionmentioning

confidence: 99%

Handling of Selenomethionines in Macromolecular Refinement

Błaszczyk¹

2014

Biochem Anal Biochem

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In the Protein Data Bank, we can find X-ray structures which were determined from selenium-derivatized proteins, but the deposited coordinates, to our surprise, contain native methionines. The problem is likely due to not complete substitution of native methionines with selenomethionines during chemical reaction. When the crystal grows from such sample, and later is subjected for X-ray analysis, it may show partial presence of native sulfur. This paper is a voice in discussion how to handle the refinement of selenomethionines. The purpose of this work is to explain why selenomethionines can't be refined purely as native methionines, particularly in macromolecular structures determined at high resolution. It is important because selenium and sulfur are different chemical elements. To explain the importance of refinement of correct atom type, author provides evidence, collected mainly from his previously reported small organic structures containing sulfur or selenium. Author emphasizes that the Xray structures, which contain selenium, are never identical with their sulfur-containing analogs. They differ at least in the respective bond lengths. Two available publicly X-ray structures have been re-refined, one small molecule and one macromolecule, in which the atom type was intentionally changed. Refinement of chemically incorrect atom type yielded non-natural behavior of atomic displacement parameters. Author concludes that the structures which contain incorrect atom types can't represent the experimental data but can serve only as models. There are examples, in the PDB, which show that selenomethionines in not fully Se-Met derivatized proteins can be refined with arbitrarily assumed fractional, less than 100%, occupancies. This inspired the author to perform various re-refinements, of the above mentioned Se-Met structure that contained S atoms in coordinates. In these re-refinements, selenomethionines are handled in different manners, and the results are compared. Author suggests refinement of chemical identities, selenium and sulfur, with fractional occupancies, as a method.

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Deoxyribonucleoside 3‘-O-(2-Thio- and 2-Oxo-“spiro”-4,4-pentamethylene-1,3,2-oxathiaphospholane)s: Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides

Cited by 117 publications

References 48 publications

Selenium Derivatization of Nucleic Acids for X‐Ray Crystal‐Structure and Function Studies

Selenium Derivatization of Nucleic Acids for X‐Ray Crystal‐Structure and Function Studies

P-Stereodefined phosphorothioate analogs of glycol nucleic acids—synthesis and structural properties

Handling of Selenomethionines in Macromolecular Refinement

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