DNA‐gesteuerte bivalente Präsentation von Liganden für den Östrogenrezeptor

Abendroth, Frank; Bujotzek, Alexander; Shan, Min; Haag, Rainer; Weber, Marcus; Seitz, Oliver

doi:10.1002/ange.201101655

Cited by 23 publications

(2 citation statements)

References 49 publications

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“…The use of hybridization to pair ligand and gain in affinity through cooperative interactions with a target is well established. [29][30][31][32][33][34] However, the majority of studies reported so far used relatively long duplexes to achieve stable pairing between ligands. We showed that in one case, this could be reduced to an extremely short length PNA oligomer (4-mer) while preserving the cooperativity.…”

Section: Resultsmentioning

confidence: 99%

PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins

Farrera-Soler

Daguer

Raunft

et al. 2020

Bioorganic & Medicinal Chemistry

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Section: Resultsmentioning

confidence: 99%

PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins

Farrera-Soler

Daguer

Raunft

et al. 2020

Bioorganic & Medicinal Chemistry

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“…¾hnlich gingen Abendroth et al bei Untersuchungen des Östrogenrezeptors vor (siehe Abbildung 14 in Abschnitt 3.2.3). [140] Die DNA-programmierte räumliche Rasterung lieferte außer dem Abstand der Konsensusbindungstaschen für Östrogen auch Hinweise auf eine zusätzliche hydrophobe Bindungsstelle auf der Oberfläche der Ligandenbindungsdomäne.…”

Section: Pna/dnaunclassified

Multivalenz als chemisches Organisations‐ und Wirkprinzip

et al. 2012

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Multivalente Wechselwirkungen können universell zur gezielten Bindungsverstärkung zwischen verschiedenen Grenzflächen oder Molekülen genutzt werden. Die Bindungspartner bilden dabei kooperativ multiple Rezeptor‐Ligand‐Wechselwirkungen, die auf einzelnen schwachen, nichtkovalenten Bindungen basieren und daher prinzipiell reversibel sind. Daher spielen multi‐ und polyvalente Wechselwirkungen in biologischen Systemen eine entscheidende Rolle für Erkennungs‐, Adhäsions‐ und Signalprozesse. Die wissenschaftliche und praktische Etablierung dieses Prinzips wird anhand der Entwicklung von natürlichen Systemen über einfache artifizielle und theoretische Modelle hin zu anwendungsorientierten funktionalen Systemen demonstriert. Anhand eines systematischen Überblicks über Gerüstarchitekturen werden die zugrunde liegenden Wirk‐ und Steuerungsmöglichkeiten aufgezeigt und Designvorschläge für möglichst effektive multivalente Bindungspartner bis hin zu polyvalenten Therapeutika aufgezeigt.

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Targeted Protein Surface Sensors as a Tool for Analyzing Small Populations of Proteins in Biological Mixtures

et al. 2014

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Optical cross-reactive sensor arrays (the so-called chemical "noses/tongues") have recently been demonstrated as a powerful tool for high-throughput protein detecting and analysis. Nevertheless, applying this technology to biomarker detection is complicated by the difficulty of non-selective sensors to operate in biological mixtures. Herein we demonstrate a step toward circumventing this limitation by using selfassembled fluorescent receptors consisting of two distinct recognition motifs: specific and non-specific. When combined in an array, binding cooperatively between the specific and non-specific protein binders enables the system to discriminate among closely related isoform biomarkers even in the presence of serum proteins or within human urine.In recent years, extensive efforts have been made to develop non-reductionist approaches to disease diagnosis. Profiling the expression of multiple proteins, rather than detecting individual protein analytes, has been explored as a means of improving diagnostic accuracy and better understanding the parameters affecting disease states.[1] A promising method for obtaining multiplexed protein analysis involves the use of antibodies that can bind and detect the proteins of interest with high affinity and selectivity. [1b,c] This approach has found widespread applications in medical diagnosis; however, the need for producing an antibody for each target and for using stepwise protocols, in addition to their relatively high costs and instability, hamper high-throughput analysis.Cross-reactive sensor arrays, inspired by the mammalian olfactory system, have recently emerged as an alternative detection method that may address these limitations. [2, 3] When the "nose/tongue" approach is used, proteins can be rapidly differentiated using an array of non-specific synthetic receptors that, in combination, generate a unique optical "fingerprint" upon interacting with each protein. Unlike antibody arrays, which operate according to the "lock and key" paradigm, arrays that rely on differential sensing [4] do not require manufacturing multiple antibodies or using technically challenging procedures. As a result, such systems can straightforwardly discriminate among multiple different proteins [3] as well as profile protein mixtures in biofluids, which may indicate disease states. [3f-i] Despite the numerous advantages of cross-reactive arrays, applications for this technology in medical diagnostics are limited by the difficulty of non-selective receptors to operate within biological mixtures. Human serum contains more than 20 000 proteins, of which only about 20 proteins constitute about 99 % of the serum protein mass. Thus, although such systems can effectively discriminate among combinations and concentrations of common serum proteins, [3g] detecting lowabundance disease biomarkers remains challenging. Herein, we present an integrated sensing scheme that uses both the "lock and key" and "differential sensing" strategies for discriminating among low-concentration pr...

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DNA‐gesteuerte bivalente Präsentation von Liganden für den Östrogenrezeptor

Cited by 23 publications

References 49 publications

PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins

PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins

Multivalenz als chemisches Organisations‐ und Wirkprinzip

Targeted Protein Surface Sensors as a Tool for Analyzing Small Populations of Proteins in Biological Mixtures

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