501088-45-5Relevant articles and documents
α- and β-Glycosyl sulfonium ions: Generation and reactivity
Nokami, Toshiki,Shibuya, Akito,Manabe, Shino,Ito, Yukishige,Yoshida, Jun-Ichi
, p. 2252 - 2255 (2009)
A study was conducted to observe the generation and reactivity of α- and β-glycosyl sulfonium ions. Preparation of a glycosyl triflate of 2-deoxy-2-amino sugar was done from a thioglycoside using glycosyl triflate pool method. The triflate oxygen was boun
Automated Quantification of Hydroxyl Reactivities: Prediction of Glycosylation Reactions
Chang, Chun-Wei,Lin, Mei-Huei,Chan, Chieh-Kai,Su, Kuan-Yu,Wu, Chia-Hui,Lo, Wei-Chih,Lam, Sarah,Cheng, Yu-Ting,Liao, Pin-Hsuan,Wong, Chi-Huey,Wang, Cheng-Chung
supporting information, p. 12413 - 12423 (2021/05/03)
The stereoselectivity and yield in glycosylation reactions are paramount but unpredictable. We have developed a database of acceptor nucleophilic constants (Aka) to quantify the nucleophilicity of hydroxyl groups in glycosylation influenced by the steric, electronic and structural effects, providing a connection between experiments and computer algorithms. The subtle reactivity differences among the hydroxyl groups on various carbohydrate molecules can be defined by Aka, which is easily accessible by a simple and convenient automation system to assure high reproducibility and accuracy. A diverse range of glycosylation donors and acceptors with well-defined reactivity and promoters were organized and processed by the designed software program “GlycoComputer” for prediction of glycosylation reactions without involving sophisticated computational processing. The importance of Aka was further verified by random forest algorithm, and the applicability was tested by the synthesis of a Lewis A skeleton to show that the stereoselectivity and yield can be accurately estimated.
Ligand design for somatostatin receptor isoforms 4 and 5
Negi, Arvind,Zhou, Jian,Sweeney, Sinclair,Murphy, Paul V.
supporting information, p. 148 - 159 (2018/12/04)
The somatostatin receptor (SSTR) isoforms, SSTR-4 and SSTR-5 are targets in numerous disorders and diseases. Although there has been some success in achieving selective isoform inhibition, structure-based drug design and development in this area has faced a challenge, mainly attributed to the lack of availability of SSTR-4 and SSTR-5 crystal structures. Previous structure activity relationship (SAR) studies have included work on non-peptide peptidomimetics or β-turn peptidal peptidomimetics where side chains of lysine, tryptophan, and phenylalanine (i.e. functional epitopes) are presented on a scaffold or molecular framework. However, there could be more structural information that would help design ligands selective for one or more of these isoforms. Here, we include synthesis of new mimetics and include their evaluation as ligands for SSTR-4 and SSTR-5. Inhibitors based on small to larger sized scaffolds (ManNAc, iminosugars, Eannaphane macrocycles, acyclic and cyclised peptide structures) are compared. These scaffolds have been grafted with side chains of lysine, tryptophan, and phenylalanine or similar bioisosteres/pharmacophoric groups. A new macrocycle as well as an iminosugar derivative show 5-fold or greater selectivity for SSTR-4 over SSTR-5. A new glycopeptide presenting GlcNAc showed ～6 fold selectivity for SSTR-5, which contrasted with the non-glycosylated peptide. A number of non-peptide dual inhibitors (Ki values of 0.58 μM to 5 μM) were also identified. Conceivable molecular interactions of these inhibitors were studied with newly constructed homology models of SSTR-4 and SSTR-5 isoforms.
Total Synthesis of the Congested, Bisphosphorylated Morganella morganii Zwitterionic Trisaccharide Repeating Unit
Keith, D. Jamin,Townsend, Steven D.
, p. 12939 - 12945 (2019/08/22)
Zwitterionic polysaccharides (ZPSs) activate T-cell-dependent immune responses by major histocompatibility complex class II presentation. Herein, we report the first synthesis of a Morganella morganii ZPS repeating unit as an enabling tool in the synthesis of novel ZPS materials. The repeating unit incorporates a 1,2-cis-α-glycosidic bond; the problematic 1,2-trans-galactosidic bond, Gal-β-(1 → 3)-GalNAc; and phosphoglycerol and phosphocholine residues which have not been previously observed together as functional groups on the same oligosaccharide. The successful third-generation approach leverages a first in class glycosylation of a phosphoglycerol-functionalized acceptor. To install the phosphocholine unit, a highly effective phosphocholine donor was synthesized.
