Publications by authors named "S V Tsukanov"

Background: Peutz-Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the growth of hamartomatous polyps in the gastrointestinal tract, perioral pigmentation and an increased risk of malignant neoplasms. The syndrome is caused by a pathogenic variant in the gene.

Aim: To assess the clinical picture and treatment of Russian patients with PJS.

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This study focused on investigating diketopiperazine (DKP) and the formation of associated double-amino-acid deletion impurities during linear solid-phase peptide synthesis (SPPS) of tirzepatide (TZP). We identified that the DKP formation primarily occurred during the Fmoc-deprotection reaction and post-coupling aging of the unstable Fmoc-Pro-Pro-Ser-resin active pharmaceutical ingredient (API) intermediate. Similar phenomena have also been observed for other TZP active pharmaceutical ingredient (API) intermediates that contain a penultimate proline amino acid, such as Fmoc-Ala-Pro-Pro-Pro-Ser-resin, Fmoc-Pro-Pro-Pro-Ser-resin, and Fmoc-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-resin, which are intermediates for both hybrid and linear synthesis approaches.

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Herein, a one-pot liquid phase peptide synthesis featuring iterative addition of amino acids to a "nanostar" support, with organic solvent nanofiltration (OSN) for isolation of the growing peptide after each synthesis cycle is reported. A cycle consists of coupling, Fmoc removal, then sieving out of the reaction by-products via nanofiltration in a reactor-separator, or synthesizer apparatus where no phase or material transfers are required between cycles. The three-armed and monodisperse nanostar facilitates both efficient nanofiltration and real-time reaction monitoring of each process cycle.

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Article Synopsis
  • The aza-Henry reaction can be risky when scaling up due to hazards from peracids and nitroalkanes, leading to the need for safer alternatives.
  • A new continuous and scalable platform was developed to create aliphatic nitroalkanes by oxidizing oximes using peracetic acid, which allows direct use of the nitroalkane in the aza-Henry reaction.
  • The innovative pipe-in-series reactor improves safety and efficiency, enabling the production of purified nitroalkane solutions for enantioselective reactions while avoiding dangerous intermediate isolation.
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Mitomycin C (MC) is an anticancer agent that alkylates DNA to form monoadducts and interstrand cross-links. Decarbamoylmitomycin C (DMC) is an analogue of MC lacking the carbamate on C10. The major DNA adducts isolated from treatment of culture cells with MC and DMC are N-deoxyguanosine (dG) adducts and adopt an opposite stereochemical configuration at the dG-mitosene bond.

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