One-bead-one-compound screening approach to the identification of cyclic peptoid inhibitors of cyclophilin D as neuroprotective agents from mitochondrial dysfunction

Hyun, Soonsil; Park, Namjoon; Nam, So Hee; Cheon, Dae Hee; Lee, Yan; Lim, Hyun‐Suk; Yu, Jaehoon

doi:10.1039/d0cc08268f

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…Finally, we used special beads to prove the success of our custom robotic systems as well as the software design and command sequences, although many other OBOC combinatorial strategies have been used extensively in drug candidates discovery during the past decades. 21,22…”

Section: Resultsmentioning

confidence: 99%

“…18–20 In particular, one-bead one-compound (OBOC) libraries have become a powerful tool in the process of lead compounds discovery because of the high structural diversity obtained by the split-and-pool method. 21–26 When automated synthesis is designed for combinatorial libraries, they can be used to produce many new compounds, which are then subsequently available for drug candidates discovery by high-throughput screening. 27–30 Thus far, several OBOC-based combinatorial libraries have been reported to solve the large demand for new drug candidates.…”

Section: Introductionmentioning

confidence: 99%

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A robotic system for automated chemical synthesis of therapeutic agents

Bao,

Yoon,

Ahn

et al. 2024

Mater. Adv.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A robotic system for automated chemical synthesis of therapeutic agents

Bao,

Yoon,

Ahn

et al. 2024

Mater. Adv.

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“…The study afforded several hits, with the most promising one having the substitution pattern shown in Figure 5. This compound inhibits the CypD‐mediated opening of the mPTP, as shown by the recovery of the mitochondrial membrane potential recovery in neuroblastoma cells [89] …”

Section: Non‐immunosuppressive Cyclooligopeptides Derived From Cyclos...mentioning

confidence: 99%

Non‐Immunosuppressive Cyclophilin Inhibitors

2022

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Cyclophilins, enzymes with peptidyl-prolyl cis/trans isomerase activity, are relevant to a large variety of biological processes. The most abundant member of this enzyme family, cyclophilin A, is the cellular receptor of the immunosuppressive drug cyclosporine A (CsA). As a consequence of the pathophysiological role of cyclophilins, particularly in viral infections, there is a broad interest in cyclophilin inhibition devoid of immunosuppressive activity. This Review first gives an introduction into the physiological and pathophysiological roles of cyclophilins. The presentation of non-immunosuppressive cyclophilin inhibitors will commence with drugs based on chemical modifications of CsA. The naturally occurring macrocyclic sanglifehrins have become other lead structures for cyclophilin-inhibiting drugs. Finally, de novo designed compounds, whose structures are not derived from or inspired by natural products, will be presented. Relevant synthetic concepts will be discussed, but the focus will also be on biochemical studies, structure-activity relationships, and clinical studies.

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“…Die Studie ergab mehrere Treffer, von denen der vielversprechendste das in Abbildung 5 dargestellte Substitutionsmuster aufweist. Diese Verbindung inhibiert die CypD‐vermittelte Öffnung der mPTP, wie die Erholung des mitochondrialen Membranpotenzials in Neuroblastomzellen zeigt [89] …”

Section: Nicht‐immunsuppressive Cyclooligopeptide Abgeleitet Von Cycl...unclassified

Nicht‐immunsuppressive Cyclophilin‐Inhibitoren

2022

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Cyclophiline, Enzyme mit einer Peptidyl-Prolyl-cis/trans-Isomerase-Aktivität, sind für eine Vielzahl biologischer Prozesse von Bedeutung. Das am häufigsten vorkommende Mitglied dieser Enzymfamilie, Cyclophilin A, ist der zelluläre Rezeptor des Immunsuppressivums Cyclosporin A (CsA). Aufgrund der pathophysiologischen Rolle der Cyclophiline, insbesondere bei Virusinfektionen, besteht ein breites Interesse an der Inhibierung von Cyclophilinen ohne immunsuppressive Wirkung. In diesem Überblick wird zunächst eine Einführung in die physiologische und pathophysiologische Rolle der Cyclophiline gegeben. Die Präsentation der nicht-immunsuppressiven Cyclophilin-Inhibitoren beginnt mit Wirkstoffen, die auf chemischen Modifikationen von CsA basieren. Die makrocyclischen, natürlich vorkommenden Sanglifehrine wurden zu einer weiteren Leitstruktur für Cyclophilin-inhibierende Wirkstoffe. Schließlich werden de novo entwickelte Verbindungen vorgestellt, deren Strukturen nicht von Naturstoffen abgeleitet oder durch sie inspiriert sind. Es werden relevante synthetische Konzepte erörtert, jedoch liegt auch ein Schwerpunkt auf biochemischen Untersuchungen, Struktur-Wirkungs-Beziehungen und klinischen Studien.

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One-bead-one-compound screening approach to the identification of cyclic peptoid inhibitors of cyclophilin D as neuroprotective agents from mitochondrial dysfunction

Abstract: The novel cyclic peptoid I11, identified from the OBOC library, promotes recovery of damaged mitochondria via binding to CypD, rejuvenating mitochondrial function without toxicity.

Cited by 6 publications

References 28 publications

A robotic system for automated chemical synthesis of therapeutic agents

A robotic system for automated chemical synthesis of therapeutic agents

Non‐Immunosuppressive Cyclophilin Inhibitors

Nicht‐immunsuppressive Cyclophilin‐Inhibitoren

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