Organoselenium compounds in medicinal chemistry

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(17)

Published: May 23, 2024

Abstract The chemical and biological interest in this element the molecules bearing selenium has been exponentially growing over years. Selenium, formerly designated as a toxin, becomes vital trace for life that appears selenocysteine its dimeric form, selenocystine, active sites of selenoproteins, which catalyze wide variety reactions, including detoxification reactive oxygen species modulation redox activities. From point view drug developments, organoselenium drugs are isosteres sulfur‐containing oxygen‐containing with advantage presence atom confers antioxidant properties high lipophilicity, would increase cell membrane permeation leading to better oral bioavailability. This statement is paramount relevance considering big number clinically employed compounds sulfur or atoms their structures nucleosides carbohydrates. Thus, article we have focused on relevant features application medicinal chemistry. With increasing chemistry, attempted highlight most significant published data subject, mainly concentrating analysis last In consequence, recent advances pharmacological discussed.

Language: Английский

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A Fluorinated Sialic Acid Vaccine Lead Against Meningitis B and C

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(22), P. 15366 - 15375

Published: May 20, 2024

Inspired by the specificity of α-(2,9)-sialyl epitopes in bacterial capsular polysaccharides (CPS), a doubly fluorinated disaccharide has been validated as vaccine lead against Neisseria meningitidis serogroups C and/or B. Emulating importance fluorine drug discovery, this molecular editing approach serves multitude purposes, which range from controlling α-selective chemical sialylation to mitigating competing elimination. Conjugation disialoside with two carrier proteins (CRM197 and PorA) enabled semisynthetic be generated; was then investigated six groups mice. The individual levels antibodies formed were compared classified highly glycan-specific protective. All glycoconjugates induced stable long-term IgG response binding native CPS epitope achieved. generated protective MenC MenB; vitro SBA OPKA assays. By merging glycan an outer cell membrane protein MenB, bivalent both created. It is envisaged that validation synthetic, bioisostere potent antigen will open new therapeutic avenues.

Language: Английский

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Chemical Synthesis Creates Single Glycoforms of the Ectodomain of Herpes Simplex Virus-1 Glycoprotein D

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(4), P. 2615 - 2623

Published: Dec. 20, 2023

Herpes simplex virus-1 (HSV-1) utilizes multiple viral surface glycoproteins to trigger virus entry and fusion. Among these glycoproteins, glycoprotein D (gD) functions as a receptor-binding protein, which makes it an attractive target for the development of vaccines against HSV-1 infection. Several recombinant gD subunit have been investigated in both preclinical clinical phases with varying degrees success. It is fundamentally critical explore glycans. In light this, we report efficient synthetic platform construct glycosylated gDs bearing homogeneous glycans at N94 N121. The oligosaccharides were prepared by enzymatic synthesis conjugated peptidyl sectors. constructed via combination 7-(piperazin-1-yl)-2-(methyl)quinolinyl (PPZQ)-assisted expressed protein ligation β-mercapto amino acid-assisted-desulfurization strategies. Biological studies showed that exhibited potent vivo activity mice.

Language: Английский

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2,2-Dichloro-1,3-benzodioxole as a Hydroxyl Protection Reagent for Carbohydrate Compounds

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

The application of 2,2-dichloro-1,3-benzodioxole (DCBZ) as a versatile hydroxyl protection reagent in carbohydrate chemistry has been demonstrated. DCBZ exhibited high reactivity with diverse vicinal and remote dihydroxyl groups furanoses pyranoses to form benzodioxole (BZDO)-protected products. BZDO group showed remarkable stability under basic, redox, glycosylation conditions can be efficiently removed acid the presence diol, highlighting its utility orthogonal synthesis complex glycans.

Language: Английский

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Synthesis of Fluorinated Glycotope Mimetics Derived from Streptococcus pneumoniae Serotype 8 CPS

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1535 - 1535

Published: Feb. 12, 2025

Fluorination of carbohydrates is a promising strategy to produce glycomimetics with improved pharmacological properties, such as increased metabolic stability, bioavailability and protein-binding affinity. Fluoroglycans are not only interest inhibitors chemical probes but increasingly being used develop potential synthetic vaccine candidates for cancer, HIV bacterial infections. Despite their attractiveness, the synthesis fluorinated oligosaccharides still challenging, emphasizing need efficient protocols that allow site-specific incorporation fluorine atoms (especially at late stages synthesis). This particularly true development fully candidates, whose (modified) carbohydrate antigen structures (glycotopes) per se comprise multistep routes. Based on known minimal protective epitope from capsular polysaccharide S. pneumoniae serotype 8, panel six novel F-glycotope mimetics was synthesized, equipped amine linkers subsequent conjugation immunogens. Next stepwise assembly via building blocks, corresponding 6F-substituted derivatives could be obtained by microwave-assisted, nucleophilic late-stage fluorination tri- tetrasaccharidic precursors in high yields. The described allowed preparation targeted sufficient quantities future immunological studies.

Language: Английский

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The Effect of Hyperconjugation and Hydrogen Bonding on the Conformers of Methylated Monosaccharides

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Abstract The conformational landscapes of four 1‐O‐methylated monosaccharides—methyl α‐glucose, methyl β‐glucose, α‐galactose, and β‐galactose—were characterized using jet‐cooled broadband rotational spectroscopy, supported by density functional theory calculations. A newly designed, simple pulsed nozzle assembly was used to introduce the sugar samples into a jet expansion without thermal degradation, eliminating need for complex expensive laser ablation system. Ten conformers were experimentally identified assigning their spectra, intricate internal rotation splittings analysed. Notably, methylation alters directionality intramolecular hydrogen bonding α‐galactose highlighting its impact on structural preference. Natural bond orbital, intrinsic strength, non‐covalent interaction analyses conducted explore interplay between hyperconjugation. set σ σ* neutral hyperconjugative interactions found override strong bond, driving preference gauche conformers.

Language: Английский

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On the influence of solvent on the stereoselectivity of glycosylation reactions

Carbohydrate Research, Journal Year: 2023, Volume and Issue: 535, P. 109010 - 109010

Published: Dec. 13, 2023

Methodology development in carbohydrate chemistry entails the stereoselective formation of C–O bonds as a key step synthesis oligo- and polysaccharides. The anomeric selectivity glycosylation reaction is affected by multitude parameters, such nature donor acceptor, activator/promotor system, temperature solvent. influence different solvents on outcome reactions employing thioglucopyranosides glycosyl donors with non-participating protecting group at position 2 has been studied. A large change function solvent was observed correlation between Kamlet-Taft parameter π* found. Furthermore, molecular modeling using density functional theory methodology conducted to decipher role possible pathways were investigated.

Language: Английский

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Development of a Cryogenic Flow Reactor to Optimize Glycosylation Reactions Based on the Active Donor Intermediate

Organic Process Research & Development, Journal Year: 2024, Volume and Issue: 28(7), P. 2819 - 2826

Published: June 11, 2024

The development of a continuous flow reactor for stereospecific glycosylation reactions with deoxy sugars is described. This apparatus that permits optimizing the selectivity based on stability activated intermediate By coupling HPLC analysis, we can optimize yield TsCl-mediated

Language: Английский

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