Mit Peptiden dekorierte Dendrimere und ihre biotechnologische Nutzung

Unsere sich stetig erweiternden Kenntnisse über biologische Systeme haben eine Vielzahl an hoch interessanten neuen biologischen Zielstrukturen aufgedeckt, deren Modulation möglicherweise neuartige Therapiemöglichkeiten für viele Krankheiten erschließt. Diese Angriffspunkte umfassen insbesondere Protein‐Protein‐ und Protein‐Nukleinsäure‐Wechselwirkungen, die jedoch durch klassische niedermolekulare Substanzen oftmals nicht adressierbar sind. Andere Substanzklassen oder Modalitäten werden daher benötigt, um diese Ziele anzuvisieren. Einige akademische Forschungsgruppen und pharmazeutische Unternehmen greifen daher zunehmend das Konzept der so genannten “neuen Modalitäten” auf. Dieser Aufsatz definiert erstmals diesen Begriff, der neuartige Peptidgerüststrukturen, Oligonukleotide, Hybride, molekulare Konjugate sowie auf neuartige Weise eingesetzte, klassische niedermolekulare Verbindungen berücksichtigt. Wir stellen die repräsentativsten Beispiele dieser Modalitäten vor, die auf große Bindungsoberflächen, wie sie in Protein‐Protein‐Wechselwirkungen vorkommen, sowie auf zentrale biologische Zellregulationsvorgänge abzielen.

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Neue Modalitäten für schwierige Zielstrukturen in der Wirkstoffentwicklung

Valeur

Guéret

Adihou

et al. 2017

Angewandte Chemie

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Branched Multimeric Peptides as Affinity Reagents for the Detection of α‐Klotho Protein

Zhang

Wang

et al. 2023

Angewandte Chemie

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α‐Klotho, an aging‐related protein found in the kidney, parathyroid gland, and choroid plexus, acts as an essential co‐receptor with the fibroblast growth factor 23 receptor complex to regulate serum phosphate and vitamin D levels. Decreased levels of α‐Klotho are a hallmark of age‐associated diseases. Detecting or labeling α‐Klotho in biological milieu has long been a challenge, however, hampering the understanding of its role. Here, we developed branched peptides by single‐shot parallel automated fast‐flow synthesis that recognize α‐Klotho with improved affinity relative to their monomeric versions. These peptides were further shown to selectively label Klotho for live imaging in kidney cells. Our results demonstrate that automated flow technology enables rapid synthesis of complex peptide architectures, showing promise for future detection of α‐Klotho in physiological settings.

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New Modalities for Challenging Targets in Drug Discovery

et al. 2017

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Our ever-increasing understanding of biological systems is providing a range of exciting novel biological targets, whose modulation may enable novel therapeutic options for many diseases. These targets include protein-protein and protein-nucleic acid interactions, which are, however, often refractory to classical small-molecule approaches. Other types of molecules, or modalities, are therefore required to address these targets, which has led several academic research groups and pharmaceutical companies to increasingly use the concept of so-called "new modalities". This Review defines for the first time the scope of this term, which includes novel peptidic scaffolds, oligonucleotides, hybrids, molecular conjugates, as well as new uses of classical small molecules. We provide the most representative examples of these modalities to target large binding surface areas such as those found in protein-protein interactions and for biological processes at the center of cell regulation.

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Mit Peptiden dekorierte Dendrimere und ihre biotechnologische Nutzung

Cited by 6 publications

References 112 publications

Neue Modalitäten für schwierige Zielstrukturen in der Wirkstoffentwicklung

Neue Modalitäten für schwierige Zielstrukturen in der Wirkstoffentwicklung

Branched Multimeric Peptides as Affinity Reagents for the Detection of α‐Klotho Protein

New Modalities for Challenging Targets in Drug Discovery

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