54400-77-0Relevant articles and documents
Glycosyl Aldehydes: New Scaffolds for the Synthesis of Neoglycoconjugates via Bioorthogonal Oxime Bond Formation
Reina, José J.,Rioboo, Alicia,Montenegro, Javier
, p. 831 - 845 (2018/01/11)
The straightforward preparation of glycosyl neoconjugates by oxime (or hydrazone) bond formation represents a key bioorthogonal tool in chemical biology. However, when this strategy is employed by reacting the reducing end of the glycan moiety, the configuration and the stereochemical information is lost due to partial (or complete) opening of the glycan cyclic hemiacetal and the formation of the corresponding opened tautomers. We have completed the synthesis of a library of glycosyl aldehydes to be used as scaffold for the synthesis of neoglycoconjugates via oxime bond formation. These glycosyl aldehydes constitute a simple and accessible alternative to avoid loss of chiral information when conjugating, by oxime (or hydrazone) bonds, the aldehyde functionality present at the reducing end of natural carbohydrates.
Synthesis and biological evaluation of novel mono- and bivalent ASGP-R-targeted drug-conjugates
Petrov, Rostislav A.,Maklakova, Svetlana Yu.,Ivanenkov, Yan A.,Petrov, Stanislav A.,Sergeeva, Olga V.,Yamansarov, Emil Yu.,Saltykova, Irina V.,Kireev, Igor I.,Alieva, Irina B.,Deyneka, Ekaterina V.,Sofronova, Alina A.,Aladinskaia, Anastasiia V.,Trofimenko, Alexandre V.,Yamidanov, Renat S.,Kovalev, Sergey V.,Kotelianski, Victor E.,Zatsepin, Timofey S.,Beloglazkina, Elena K.,Majouga, Alexander G.
, p. 382 - 387 (2017/12/26)
Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC.
Why Is Direct Glycosylation with N-Acetylglucosamine Donors Such a Poor Reaction and What Can Be Done about It?
Marqvorsen, Mikkel H. S.,Pedersen, Martin J.,Rasmussen, Michelle R.,Kristensen, Steffan K.,Dahl-Lassen, Rasmus,Jensen, Henrik H.
, p. 143 - 156 (2017/04/26)
The monosaccharide N-acetyl-d-glucosamine (GlcNAc) is an abundant building block in naturally occurring oligosaccharides, but its incorporation by chemical glycosylation is challenging since direct reactions are low yielding. This issue, generally agreed upon to be caused by an intermediate 1,2-oxazoline, is often bypassed by introducing extra synthetic steps to avoid the presence of the NHAc functional group during glycosylation. The present paper describes new fundamental mechanistic insights into the inherent challenges of performing direct glycosylation with GlcNAc. These results show that controlling the balance of oxazoline formation and glycosylation is key to achieving acceptable chemical yields. By applying this line of reasoning to direct glycosylation with a traditional thioglycoside donor of GlcNAc, which otherwise affords poor glycosylation yields, one may obtain useful glycosylation results.
