Stereoselective sulfoxide formation from a thioproline derivative

Kánai, Károly; Podányi, Benjamin; Bokotey, Sándor; Hajdú, Félix; Hermecz, István

doi:10.1016/s0957-4166(02)00134-9

Cited by 5 publications

(8 citation statements)

References 18 publications

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“…Sulfides can be oxidized by other dioxygenases, such as thymine hydroxylase (66), 4-hydroxyphenylpyruvate dioxygenase (67), and cysteine dioxygenase (68). Although the chemical oxidation of Thp produces both sulfoxide diastereomers (50), turnover by P4H produces only the 4 R sulfoxide, which has the same relative stereochemistry as the natural product, Hyp. α-Ketoglutarate is decarboxylated when Thp, flp, or Pro is the substrate in a reaction with P4H (Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…A mixture of PEG-Gly–Tyr–Thp(O)–GlyOEt and PEG-Gly–Tyr–thp(O)–GlyOEt was produced by chemical oxidation of the Thp-containing peptide with either 3-chloroperoxybenzoic acid (MCPBA) (1 equiv) in chloroform for 2.5 h at room temperature or sodium periodate (1.1 equiv) in aqueous methanol (75%) for 30 min at 50 °C (50). A peptide containing Thp(O,O) was produced by reaction of the Thp-containing peptide with MCPBA (10 equiv) in chloroform for 5 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

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Conformational Preferences of Substrates for Human Prolyl 4-Hydroxylase

et al. 2008

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Prolyl 4-hydroxylase (P4H) catalyzes the post-translational hydroxylation of (2S)-proline (Pro) residues in procollagen strands. The resulting (2S,4R)-4-hydroxyproline (Hyp) residues are essential for the folding, secretion, and stability of the collagen triple helix. Even though its product (Hyp) differs from its substrate (Pro) by only a single oxygen atom, no product inhibition has been observed for P4H. Here, we examine the basis for the binding and turnover of substrates by human P4H. Synthetic peptides containing (2S,4R)-4-fluoroproline (Flp), (2S,4S)-4-fluoroproline (flp), (2S)-4-ketoproline (Kep), (2S)-4-thiaproline (Thp), and 3,5-methanoproline (Mtp) were evaluated as substrates for P4H. Peptides containing Pro, flp, and Thp were found to be excellent substrates for P4H, forming Hyp, Kep, and (2S,4R)-thiaoxoproline, respectively. Thus, P4H is tolerant to some substitutions on C-4 of the the pyrrolidine ring. In contrast, peptides containing Flp, Kep, or Mtp did not even bind to the active site of P4H. Each proline analog that does bind to P4H is also a substrate, indicating that discrimination occurs at the level of binding rather than turnover. As the iron(IV)-oxo species that forms in the active site of P4H is highly reactive, P4H has an imperative for forming a snug complex with its substrate, and appears to do so. Most notably, those proline analogs with a greater preference for a C γ -endo pucker and cis peptide bond were the ones recognized by P4H. As Hyp has a strong preference for C γ -exo pucker and trans peptide bond, P4H appears to discriminate against the conformation of proline residues in a manner that diminishes product inhibition during collagen biosynthesis.Collagens are the major structural proteins in the extracellular matrix. All collagens are comprised of three polypeptide strands that coil together into a right-handed triple helix. Each strand contains a repeating three amino-acid sequence in which every third residue is a glycine (Gly 1 ): Xaa-Yaa-Gly. The Xaa position is often (2S)-proline (Pro), and the Yaa position is often (2S,4R)-4-hydroxyproline (Hyp) (1). Hyp is produced by the action of prolyl 4-hydroxylase (P4H; EC 1.14.11.2). This post-translational modification is the most prevalent † This work was supported by Grants AR044276 (NIH to R.T.R) and CHE 0515635 (NSF to G.R.K.). K.L.G. was supported by ChemistryBiology Interface Training Grant T32 BM008505 (NIH). MALDI-MS experiments were performed at the University of WisconsinMadison Biophysics Instrumentation Facility, which was established with Grants BIR-9512577 (NSF) and RR13790 (NIH).*To whom correspondence should be addressed: Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706-1544. Telephone: 608-262-8588. Fax: 608-262-3453. rtraines@wisc.edu. NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2010 January 22. in the kingdom Animalia, where Hyp is more common than seven of the "common" aminoacid residues: Cys, Gln, His, Met, P...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Conformational Preferences of Substrates for Human Prolyl 4-Hydroxylase

et al. 2008

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“…SPro forms part of the structure of kynostatin 272 (KNI-272) a pentapeptide mimic containing two sulfur atoms that acts as a conformationally constrained inhibitor of HIV protease [ 24 , 25 , 26 , 27 , 28 ] and for which the role of the SPro residue in the conformation has been discussed [ 26 , 27 ]. In the same context, it forms part of the structure of possible prolyl-oligopeptidase inhibitors of use in the prevention of Alzheimer’s disease and senile dementia [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Decoding the Structure of Non-Proteinogenic Amino Acids: The Rotational Spectrum of Jet-Cooled Laser-Ablated Thioproline

et al. 2021

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The broadband rotational spectrum of jet-cooled laser-ablated thioproline was recorded. Two conformers of this system were observed and identified with the help of DFT and ab initio computations by comparison of the observed and calculated rotational constants and 14N quadrupole coupling constants as well as the predicted energies compared to the observed relative populations. These conformers showed a mixed bent/twisted arrangement of the five-membered ring similar to that of the related compound thiazolidine with the N–H bond in axial configuration. The most stable form had the COOH group in an equatorial position on the same side of the ring as N-H. The arrangement of the C=O group close to the N-H bond led to a weak interaction between them (classified as type I) characterized by a noncovalent interaction analysis. The second form had a trans-COOH arrangement showing a type II O–H···N hydrogen bond. In thioproline, the stability of conformers of type I and type II was reversed with respect to proline. We show how the conformation of the ring depends on the function associated with the endocyclic N atom when comparing the structures of isolated thioproline with its zwitterion observed in condensed phases and with peptide forms.

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“…The dissolved solid (in the case of compounds 2A, 2B and 2H-the details in SI) or the yellow oil (in the case of compounds 2C-2G-the details in SI) was dissolved in toluene to separate the product from insoluble impurities. The solvent was evaporated, and the product obtained was washed with warm hexane and left to dry [17]. Compound 2 was dissolved in a solution of CH 2 Cl 2 /toluene (2:1) and cooled in an ice bath.…”

Section: Synthesismentioning

confidence: 99%

Weak Interactions in the Structures of Newly Synthesized (–)-Cytisine Amino Acid Derivatives

2021

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Eight new (–)-(N-[(AA)-(N-phtaloyl)]cytisines (where AA is amino acid: glycine, β-alanine, D,L-valine, L-valine, L-isoleucine, L-leucine, D-leucine and D,L-phenyloalanine), were synthesized and fully spectroscopically characterized (NMR, FTIR and MS). For two of these compounds, N-[glycine-(N-phtaloyl)]cytisine and N-[L-isoleucine-(N-phtaloyl)]cytisine, X-ray crystal structures were obtained and used as the basis for an in-depth analysis of intermolecular interactions and packing energies. The structural geometrical data (weak hydrogen bonds, π···π interactions, etc.) were compared with the energies of interactions and the topological characteristics (electron density, Laplacian at the appropriate critical point) based on the atoms-in-molecules theory. The results suggest that there is no straightforward connection between the geometry of point-to-point interactions and the molecule-to-molecule energies. Additionally, the usefulness of the transfer of multipolar parameters in estimating of critical points’ characteristics have been confirmed.

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Stereoselective sulfoxide formation from a thioproline derivative

Cited by 5 publications

References 18 publications

Conformational Preferences of Substrates for Human Prolyl 4-Hydroxylase

Conformational Preferences of Substrates for Human Prolyl 4-Hydroxylase

Decoding the Structure of Non-Proteinogenic Amino Acids: The Rotational Spectrum of Jet-Cooled Laser-Ablated Thioproline

Weak Interactions in the Structures of Newly Synthesized (–)-Cytisine Amino Acid Derivatives

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