Carbohydrate–PNA and Aptamer–PNA Conjugates for the Spatial Screening of Lectins and Lectin Assemblies

Scheibe, Christian; Wedepohl, Stefanie; Riese, Sebastian B.; Dernedde, Jens; Seitz, Oliver

doi:10.1002/cbic.201200618

Cited by 40 publications

(35 citation statements)

References 99 publications

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“…89, 96 For example, multivalent carbohydrate displays of this type have been used to probe how the dimeric antibody 2G12 interacts with mannosylated gp120 on HIV (Figure 5). 86 Because 2G12 can neutralize HIV, it is thought that compounds that bind tightly to 2G12 might serve as haptens for the development of effective anti-HIV antibodies.…”

Section: Maximizing Protein Recognition Of Glycopolymersmentioning

confidence: 99%

Glycopolymer probes of signal transduction

2013

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Glycans are key participants in biological processes ranging from reproduction to cellular communication to infection. Revealing glycan roles and the underlying molecular mechanisms by which glycans manifest their function requires access to glycan derivatives that vary systematically. To this end, glycopolymers (polymers bearing pendant carbohydrates) have emerged as valuable glycan analogs. Because glycopolymers can readily be synthesized, their overall shape can be varied, and they can be altered systematically to dissect the structural features that underpin their activities. This review provides examples in which glycopolymers have been used to effect carbohydrate-mediated signal transduction. Our objective is to illustrate how these powerful tools can reveal the molecular mechanisms that underlie carbohydrate-mediated signal transduction.

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Section: Maximizing Protein Recognition Of Glycopolymersmentioning

confidence: 99%

Glycopolymer probes of signal transduction

2013

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“…Further, Hill plots suggest cooperative binding. 5 A different method for ON organized multivalent binding of RCA120 lectin has been recently shown by Seitz and coworkers (97) with similar results.…”

Section: Multivalent Protein Binding Via On Self Assemblymentioning

confidence: 66%

Oligonucleotide-based systems for input-controlled and non-covalently regulated protein binding

Battle¹,

Chu²,

Jayawickramarajah³

2013

Supramolecular Chemistry

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Supramolecular chemists continuously take inspiration from complex biological systems to develop functional molecules involved in molecular recognition and self-assembly. In this regard, “smart” synthetic molecules that emulate allosteric proteins are both exciting and challenging, since many allosteric proteins can be considered as molecular switches that bind to other protein targets in a non-covalent fashion, and importantly, are capable of having their output activity controlled by prior binding to input molecules. This review discusses the foundations and passage toward the development of non-covalently operated oligonucleotide-based systems with protein-binding capacity that can be precisely regulated in an input-controlled manner.

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“…Seitz and co-workers recently performed a thorough proof-of-concept study proving the usefulness of DNA as a template for creating precise multivalent architectures in a bottom-up approach (Figure 16c). 150 In this work, base pairing between DNA and synthetic peptide nucleic acids modified with N -acetyllactosamine (LacNAc) was employed to tailor scaffolds with precisely defined valency, precisely defined spacing, and varied flexibility. The binding of LacNAc to Ricinus communis agglutinin (RCA 120 ) is known, with two binding sites that are ∼130 Å apart across the concave surface of the protein.…”

Section: Approaches To Overcoming Heterogeneity Problems In Multivalementioning

confidence: 99%

Multivalent Polymers for Drug Delivery and Imaging: The Challenges of Conjugation

2014

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Multivalent polymers offer a powerful opportunity to develop theranostic materials on the size scale of proteins that can provide targeting, imaging, and therapeutic functionality. Achieving this goal requires the presence of multiple targeting molecules, dyes, and/or drugs on the polymer scaffold. This critical review examines the synthetic, analytical, and functional challenges associated with the heterogeneity introduced by conjugation reactions as well as polymer scaffold design. First, approaches to making multivalent polymer conjugations are discussed followed by an analysis of materials that have shown particular promise biologically. Challenges in characterizing the mixed ligand distributions and the impact of these distributions on biological applications are then discussed. Where possible, molecular-level interpretations are provided for the structures that give rise to the functional ligand and molecular weight distributions present in the polymer scaffolds. Lastly, recent strategies employed for overcoming or minimizing the presence of ligand distributions are discussed. This review focuses on multivalent polymer scaffolds where average stoichiometry and/or the distribution of products have been characterized by at least one experimental technique. Key illustrative examples are provided for scaffolds that have been carried forward to in vitro and in vivo testing with significant biological results.

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Carbohydrate–PNA and Aptamer–PNA Conjugates for the Spatial Screening of Lectins and Lectin Assemblies

Cited by 40 publications

References 99 publications

Glycopolymer probes of signal transduction

Glycopolymer probes of signal transduction

Oligonucleotide-based systems for input-controlled and non-covalently regulated protein binding

Multivalent Polymers for Drug Delivery and Imaging: The Challenges of Conjugation

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