Glycans in Mesoporous and Nanoporous Materials

Stine, Keith J.

doi:10.1002/9781118860212.ch9

Cited by 3 publications

(3 citation statements)

References 148 publications

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“…Many reports on the design of multivalent ligands rely on statistical polymers, whose epitope density, length, or stereochemistry are not precisely defined. 13 , 14 Thus, their presentation of glycan-binding epitopes with different geometries and orientations may preclude selective binding. We postulated that discrete synthetic glycomacromolecules with precise absolute configurations could bind lectins with higher and/or tunable selectivity.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Glycomacromolecules of Defined Valency, Absolute Configuration, and Topology Distinguish between Human Lectins

Hartweg

Jiang

Yilmaz

et al. 2021

JACS Au

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Carbohydrate-binding proteins (lectins) play vital roles in cell recognition and signaling, including pathogen binding and innate immunity. Thus, targeting lectins, especially those on the surface of immune cells, could advance immunology and drug discovery. Lectins are typically oligomeric; therefore, many of the most potent ligands are multivalent. An effective strategy for lectin targeting is to display multiple copies of a single glycan epitope on a polymer backbone; however, a drawback to such multivalent ligands is they cannot distinguish between lectins that share monosaccharide binding selectivity (e.g., mannose-binding lectins) as they often lack molecular precision. Here, we describe the development of an iterative exponential growth (IEG) synthetic strategy that enables facile access to synthetic glycomacromolecules with precisely defined and tunable sizes up to 22.5 kDa, compositions, topologies, and absolute configurations. Twelve discrete mannosylated “glyco-IEGmers” are synthesized and screened for binding to a panel of mannoside-binding immune lectins (DC-SIGN, DC-SIGNR, MBL, SP-D, langerin, dectin-2, mincle, and DEC-205). In many cases, the glyco-IEGmers had distinct length, stereochemistry, and topology-dependent lectin-binding preferences. To understand these differences, we used molecular dynamics and density functional theory simulations of octameric glyco-IEGmers, which revealed dramatic effects of glyco-IEGmer stereochemistry and topology on solution structure and reveal an interplay between conformational diversity and chiral recognition in selective lectin binding. Ligand function also could be controlled by chemical substitution: by tuning the side chains of glyco-IEGmers that bind DC-SIGN, we could alter their cellular trafficking through alteration of their aggregation state. These results highlight the power of precision synthetic oligomer/polymer synthesis for selective biological targeting, motivating the development of next-generation glycomacromolecules tailored for specific immunological or other therapeutic applications.

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Section: Introductionmentioning

confidence: 99%

Synthetic Glycomacromolecules of Defined Valency, Absolute Configuration, and Topology Distinguish between Human Lectins

Hartweg

Jiang

Yilmaz

et al. 2021

JACS Au

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“…At the end of the synthesis, the resulting glycan can be either cleaved-off for further processing or deprotected directly on the gold surface to be used for recognition studies or immunoassay development. 44 The STICS concept was developed with robotic arm automation in mind. However, we discovered that standard HPLC equipment would offer a more accessible platform for automation.…”

Section: Introductionmentioning

confidence: 99%

“…The basis for this concept is a surface-functionalized stack of nanoporous gold plates that simplifies the transfer of the gold surface-bound molecules between reaction vessels. At the end of the synthesis, the resulting glycan can be either cleaved-off for further processing or deprotected directly on the gold surface to be used for recognition studies or immunoassay development . The STICS concept was developed with robotic arm automation in mind.…”

Section: Introductionmentioning

confidence: 99%

HPLC-Assisted Automated Oligosaccharide Synthesis: Implementation of the Autosampler as a Mode of the Reagent Delivery

et al. 2016

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The development of a useful methodology for simple, scalable, and transformative automation of oligosaccharide synthesis that easily interfaces with existing methods is reported. The automated synthesis can now be performed using accessible equipment where the reactants and reagents are delivered by the pump or the autosampler and the reactions can be monitored by the UV detector. The HPLC-based platform for automation is easy to setup and adapt to different systems and targets.

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Monolayers of Carbohydrate-Containing Lipids at the Water- Air Interface

Nepal¹,

Stine²

2019

Cell Culture

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Glycolipids are important members of the glycoconjugate family that are distributed on cell surfaces and are important in aspects of cellular behavior including signal transduction, protein trafficking, cell surface recognition and cell adhesion. Errors in the synthesis or mutations of these glycoconjugates are often linked with various human pathological conditions. The complex nature of their molecular structures coupled with the complexity of cellular structure make their study a challenging process, which can be simplified by fabrication of model membrane systems. Liposomes and monolayers of lipids at the airwater interface are two of the most frequently used model membrane systems. Techniques for fabrication of monolayer models and methods used for their studies are discussed with a focus on glycolipids.

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Glycans in Mesoporous and Nanoporous Materials

Cited by 3 publications

References 148 publications

Synthetic Glycomacromolecules of Defined Valency, Absolute Configuration, and Topology Distinguish between Human Lectins

Synthetic Glycomacromolecules of Defined Valency, Absolute Configuration, and Topology Distinguish between Human Lectins

HPLC-Assisted Automated Oligosaccharide Synthesis: Implementation of the Autosampler as a Mode of the Reagent Delivery

Monolayers of Carbohydrate-Containing Lipids at the Water- Air Interface

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