41308-76-3Relevant articles and documents
Probing low affinity and multivalent interactions with surface plasmon resonance: Ligands for concanavalin A
Mann, David A.,Kanai, Motomu,Maly, Dustin J.,Kiessling, Laura L.
, p. 10575 - 10582 (1998)
The affinities of the carbohydrate-binding protein concanavalin A (Con A) for mono- and multivalent ligands were measured by surface plasmon resonance (SPR) detection. Assessing protein-carbohydrate affinities is typically difficult due to weak affinities observed and the complications that arise from the importance of multivalency in these interactions. We describe a convenient method to rapidly evaluate the inhibitory constants for a panel of different ligands, both monovalent and multivalent, for low- affinity receptors, such as the carbohydrate-binding protein Con A. A nonnatural, mannose-substituted glycolipid was synthesized, and self- assembled monolayers of varying carbohydrate density were generated. The synthetic surfaces bind Con A. Competition experiments that employed monovalent ligands in solution yielded K(i) values similar to equilibrium binding constants obtained in titration microcalorimetry experiments. In addition, this assay could be used to examine various polymeric ligands of defined lengths, generated by ring-opening metathesis polymerization (ROMP). This study demonstrates the utility of this method for rapidly screening ligands that engage in low affinity interactions with their target receptors. Our results emphasize that those molecules that can simultaneously occupy two or more saccharide binding sites within a lectin oligomer are effective inhibitors of protein-carbohydrate interactions.
Bimodal Targeting Using Sulfonated, Mannosylated PEI for Combined Gene Delivery and Photodynamic Therapy
Chitgupi, Upendra,Li, Yi,Chen, Mingfu,Shao, Shuai,Beitelshees, Marie,Tan, Myles Joshua,Neelamegham, Sriram,Pfeifer, Blaine A.,Jones, Charles,Lovell, Jonathan F.
, p. 600 - 608 (2017)
Photodynamic therapy (PDT) and gene delivery have both been used to target both cancer cells and tumor-associated macrophages (TAMs). Given the complex nature of tumor tissue, there could be merit in combining these strategies simultaneously. In this study, we developed a bimodal targeting approach to both cancer cells and macrophages, employing materials conducive to both gene delivery and PDT. Polymers libraries were created that consisted of cationic polyethyleneimine (PEI) conjugated to the photosensitizer pyropheophorbide-a, with sulfonation (to target selectin-expressing cells) and mannosylation (to target TAMs). Polyplexes, consisting of these polymers electrostatically bound to DNA, were analyzed for transfection efficacy and cytotoxicity toward epithelial cells and macrophages to assess dual-targeting. This study provides preliminary proof of principle for using modified PEI for targeted gene delivery and PDT.
Structure-function assessment of mannosylated poly(β-amino esters) upon targeted antigen presenting cell gene delivery
Jones, Charles H.,Chen, Mingfu,Gollakota, Akhila,Ravikrishnan, Anitha,Zhang, Guojian,Lin, Sharon,Tan, Myles,Cheng, Chong,Lin, Haiqing,Pfeifer, Blaine A.
, p. 1534 - 1541 (2015)
Antigen presenting cell (APC) gene delivery is a promising avenue for modulating immunological outcomes toward a desired state. Recently, our group developed a delivery methodology to elicit targeted and elevated levels of APC-mediated gene delivery. During these initial studies, we observed APC-specific structure-function relationships with the vectors used during gene delivery that differ from current non-APC cell lines, thus, emphasizing a need to re-evaluate vector-associated parameters in the context of APC gene transfer. Thus, we describe the synthesis and characterization of a second-generation mannosylated poly(β-amino ester) library stratified by molecular weight. To better understand the APC-specific structure-function relationships governing polymeric gene delivery, the library was systematically characterized by (1) polymer molecular weight, (2) relative mannose content, (3) polyplex biophysical properties, and (4) gene delivery efficacy. In this library, polymers with the lowest molecular weight and highest relative mannose content possessed gene delivery transfection efficiencies as good as or better than commercial controls. Among this group, the most effective polymers formed the smallest polymer-plasmid DNA complexes (～300 nm) with moderate charge densities (10 mV). This convergence in polymer structure and polyplex biophysical properties suggests a unique mode of action and provides a framework within which future APC-targeting polymers can be designed.
Synthesis, CI-MS analyses and preliminary biological evaluation of a novel library of hydrophobic persulfide-spacers α-alkyl glycosides
Hassan, Hammed H.A.M.
, p. 127 - 135 (2010)
We report the synthesis of novel polyether-based polyols derived from simple glycosides that bear sulfur spacers in the attempt to potentially provide new antibiotics. The CI-MS demonstrated the stepwise and successive fission of the sulfide-spacer groups; however, it does not distinguish between the alditols having different arrangement of O- (CH2)3-S(CH 2)2OH groups. The investigated compounds exhibited antimicrobial activities against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and antifungal activities against Candida albicans at a concentration of 1 mg /ml in DMF.
Anomeric alkylations and acylations of unprotected mono- and disaccharides mediated by pyridoneimine in aqueous solutions
Dey, Kalyan,Jayaraman, Narayanaswamy
supporting information, p. 2224 - 2227 (2022/02/17)
A site-specific deprotonation followed by alkylations and acylations of sugar hemiacetals to the corresponding alkyl glycosides and acylated sugars in aqueous solutions is disclosed herein. Pyridoneimine as a new base is developed to mediate the deprotonation of readily available sugar hemiacetals and further reactions with alkylation and acylation agents.
Synthesis of the hyper-branched core tetrasaccharide motif of chloroviruses
Mishra, Bijoyananda,Manmode, Sujit,Walke, Gulab,Chakraborty, Saptashwa,Neralkar, Mahesh,Hotha, Srinivas
, p. 1315 - 1328 (2021/02/26)
Chemical synthesis of complex oligosaccharides, especially those possessing hyper-branched structures with one or multiple 1,2-cisglycosidic bonds, is a challenging task. Complementary reactivity of glycosyl donors and acceptors and proper tuning of the s
Carbon tetrachloride-free allylic halogenation-mediated glycosylations of allyl glycosides
Das, Anupama,Jayaraman, Narayanaswamy
, p. 9318 - 9325 (2021/11/13)
The allylic bromination of allyl glycosides is conducted using NBS/AIBN reagents in (EtO)2CO and PhCF3 solutions, without using CCl4 as a solvent. The activated mixed halo-allyl glycosides led to glycosylations, mediated by a triflate, in a latent-active
Synthesis, Conformational Analysis, and Complexation Study of an Iminosugar-Aza-Crown, a Sweet Chiral Cyclam Analog
Ardá, Ana,Blériot, Yves,Bordes, Alexandra,Désiré, Jér?me,Franconetti, Antonio,Guillard, Jer?me,Jiménez-Barbero, Jesús,Ménand, Micka?l,Perrin, Flavie,Poveda, Ana,Sollogoub, Matthieu,Tripier, Rapha?l,Troadec, Thibault
supporting information, (2020/03/26)
A new family of chiral C2 symmetric tetraazamacrocycles, coined ISAC for IminoSugar Aza-Crown, incorporating two iminosugars adopting a 4C1 conformation is disclosed. Multinuclear NMR experiments on the corresponding Cdsu
Total Synthesis of 6-Amino-2,6-dideoxy-α-Kdo from d -Mannose
Ameur, Nassima,Gamboa Marin, Oscar Javier,Gauthier, Charles,Gormand, Paul,Hussain, Nazar,Ravicoularamin, Gokulakrishnan,Sauvageau, Janelle
supporting information, (2020/07/27)
3-Deoxy-d-manno-oct-2-ulosonic acid (Kdo) biosynthetic pathway is a promising target in antibacterial drug discovery. Herein, we report the total synthesis of 6-amino-2,6-dideoxy-α-Kdo in 15 steps from d-mannose as a potential inhibitor of Kdo-processing
Automated Solution-Phase Synthesis of S-Glycosides for the Production of Oligomannopyranoside Derivatives
Kern, Mallory K.,Pohl, Nicola L. B.
supporting information, (2020/06/08)
Thioglycosides are more resistant to enzymatic hydrolysis than their O-linked counterparts, thereby becoming attractive targets for carbohydrate-based therapeutic development. We report the first development of methods for the site-selective incorporation
