1240485-59-9Relevant academic research and scientific papers
Synthesis of Protected 3,4- And 2,3-Dimercaptophenylalanines as Building Blocks for Fmoc-Peptide Synthesis and Incorporation of the 3,4-Analogue in a Decapeptide Using Solid-Phase Synthesis
Banerjee, Isita,Ghosh, Keshab Ch.,Oheix, Emmanuel,Jean, Marion,Naubron, Jean-Valère,Réglier, Marius,Iranzo, Olga,Sinha, Surajit
, p. 2210 - 2223 (2021)
3,4-Dimercaptophenylalanines and 2,3-dimercaptophenylalanines have been synthesized for the first time by nucleophilic substitution of a protected aminomalonate on 3,4- and 2,3-dimercaptobenzyl bromide derivatives. The dithiol functions were protected as thioketals, and the key precursors, diphenylthioketal-protected dimercaptobenzyl bromides, were synthesized via two distinct routes from either dihydroxy benzoates or toluene-3,4-dithiol. Racemic mixtures of the fully protected amino acids were separated by chiral HPLC into the corresponding enantiomers. The absolute configuration of both 3,4- and 2,3-analogues could be assigned based on X-ray crystallography and VCD/DFT measurements. Thioketal groups were deprotected upon reaction with mercury oxide and aqueous tetrafluoroboric acid followed by treatment with H2S gas under an argon atmosphere to obtain the corresponding dimercapto amino acids. The optically pure l-Fmoc-protected 3,4-analogue (S- enantiomer) was successfully incorporated into a decapeptide using standard solid-phase peptide synthesis. Therefore, dithiolene-functionalized peptides are now accessible from a simple synthetic procedure, and this should afford new molecular tools for research into the catalysis, diagnostic, and nanotechnology fields.
Bioorthogonal Ligation and Cleavage by Reactions of Chloroquinoxalines with ortho-Dithiophenols
Fu, Hua,Li, Hongyun,Li, Youshan,Lou, Zhenbang,Yang, Haijun,Zhao, Yufen
, p. 3671 - 3677 (2020/02/04)
A bioorthogonal ligation and cleavage method via reactions of chloroquinoxalines (CQ) and ortho-dithiophenols (DT) is presented. Double nucleophilic substitutions of ortho-dithiophenols to chloroquinoxalines provide conjugates containing tetracyclic benzo[5,6][1,4]dithiino[2,3-b]quinoxaline with strong built-in fluorescence together with release of the other functional molecules. Three cleavable linkers were designed and successfully used in release of the molecules containing biotin from the protein conjugates. The CQ-DT bioorthogonal reactions can be applied for the bioorthogonal ligations, bioorthogonal cleavages, and trans-tagging of proteins, and show advantages of readily accessible unnatural orthogonal groups, appealing reaction kinetics (k2≈1.3 m?1 s?1), excellent biocompatibility of orthogonal groups, and high stability of conjugates. This complements previous bioorthogonal reactions and is a new route for protein-fishing applications and in-gel fluorescence analysis.
Cell-Penetrating Dynamic-Covalent Benzopolysulfane Networks
Cheng, Yangyang,Zong, Lili,López-Andarias, Javier,Bartolami, Eline,Okamoto, Yasunori,Ward, Thomas R.,Sakai, Naomi,Matile, Stefan
, p. 9522 - 9526 (2019/06/24)
Cyclic oligochalcogenides (COCs) are emerging as promising systems to penetrate cells. Clearly better than and different to the reported diselenolanes and epidithiodiketopiperazines, we introduce the benzopolysulfanes (BPS), which show efficient delivery, insensitivity to inhibitors of endocytosis, and compatibility with substrates as large as proteins. This high activity coincides with high reactivity, selectively toward thiols, exceeding exchange rates of disulfides under tension. The result is a dynamic-covalent network of extreme sulfur species, including cyclic oligomers, from dimers to heptamers, with up to nineteen sulfurs in the ring. Selection from this unfolding adaptive network then yields the reactivities and selectivities needed to access new uptake pathways. Contrary to other COCs, BPS show high retention on thiol affinity columns. The identification of new modes of cell penetration is important because they promise new solutions to challenges in delivery and beyond.
