Isolation and Structure Elucidation of Chlorofusin, a Novel p53-MDM2 Antagonist from a Fusarium sp. [J. Am. Chem. Soc. 2001, 123, 554−560].

Duncan, Sara J.; Grüschow, Sabine; Williams, Dudley H.; McNicholas, Carole; Purewal, Ravinder; Hajek, Michaela; Gerlitz, Martin; Martin, Steven; and, Stephen K. Wrigley; Moore, Michael

doi:10.1021/ja025114k

Cited by 13 publications

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“…This connectivity is confirmed by HMBC correlations CH(2)-CH(1; 71.53) and CH(2)-CH 2 (5,9; 23.10). CH(1) has further vicinal COSY correlations to CH 2 (3,10), which in turn has a vicinal correlation to CH (6). The connectivity in updated fragment 9 is supported by HMBC correlations CH(8)-CH 2 (3,10; 45.03) and CH(1)-CH(6; 31.62).…”

Section: Example: Structural Connectivity Of Mentholmentioning

confidence: 92%

“…HMBC (or A number of small preliminary fragments can quickly be generated. The HMBC correlations between singlet CH 3 (6) and C(171.75) suggests methyl ester fragment 28, whereas the correlation between singlet CH 3 (13), appearing at δ = 1.90 ppm, and C(169.66) suggests acetate fragment 29. CH 3 (19) and CH 3 Although CH 2 (8,18) has no further COSY correlations, suggesting no adjacent protons, it does have HMBC correlations to C(35.52) and CH 3 (19), intercepting fragment 30.…”

Section: Case Study: Salvinorin Amentioning

confidence: 97%

“…CH(6) has a vicinal COSY correlation to CH 3 (12), but further correlations are obscured by spectral overlap. However, CH (6) has an HMBC correlation to CH 2 (4,13; 34.51), indicating fragment 10. This incorporates all the atoms in the molecule.…”

Section: Example: Structural Connectivity Of Mentholmentioning

confidence: 99%

“…Recent work has uncovered the structural details of not only natural products of every class but also synthetic creations. Well-characterized examples include platensimycin (1), [4] a broad spectrum nonmevalonate terpenoid antibiotic, maoecrystal V (2), [5] an antitumor diterpenoid, chlorofusin, a peptide-based fungal metabolite with anticancer properties, [6] daphlongeranine B (3), [7] an unusual polycyclic alkaloid, and cytosporic acid (4), [8] a polyketide-derived HIV-1 integrase inhibitor, as well as β,βЈ-disilyl-substituted vinyl cations 5 [9] and cyanoresorc [5]arene 6. [10] For simple unknowns, straightforward experiments such as 1D 1 H and 13 C NMR, COSY (correlation spectroscopy), and NOESY (nuclear Overhauser spectroscopy) suffice.…”

Section: Introductionmentioning

confidence: 99%

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Structural Elucidation with NMR Spectroscopy: Practical Strategies for Organic Chemists

2008

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Practical strategies for the structural elucidation of small organic molecules are described for typical organic chemists. The analysis of an unknown is divided into three stages. First, structural connectivity is deduced from through‐bond correlation experiments. Next, the relative stereochemistry is determined from NOE correlations and coupling constants (both proton–proton and proton–carbon). Finally, the proposed structure is verified by a careful inspection of all of the observed data. Tactics for the management of overlapping peaks, low sample concentrations, and high molecular weights are also described. This approach is illustrated by the step‐by‐step analyses of a simple test compound, menthol, and a complex polycyclic natural product, salvinorin A. Detailed procedures and sample data for menthol are provided as a practical tutorial. This will enable organic chemists to elucidate a wide range of complex structures by using modern NMR spectroscopic experiments.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

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Section: Example: Structural Connectivity Of Mentholmentioning

confidence: 92%

Section: Case Study: Salvinorin Amentioning

confidence: 97%

Section: Example: Structural Connectivity Of Mentholmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structural Elucidation with NMR Spectroscopy: Practical Strategies for Organic Chemists

2008

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“…6 Numerous studies have been successful in disrupting the mdm2:p53 interaction using inhibitory peptides, 7 ' 8 peptide analogs, 9 ' 11 or polycyclic compounds. 12 " 16 These inhibitors target the deep hydrophobic cleft of mdm2 that interacts with the N-terminal a-helix of p53.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-Mediated Rescue of p53 Through Targeted Degradation of MDM2

Fischer¹

2006

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SUPPLEMENTARY NOTES 12a. DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited 12b. DISTRIBUTION CODE ABSTRACT (Maximum 200 Words)The interaction between mdm2 and p53 is a viable therapeutic target, as overexpression of mdm2 can lead to excessive p53 degradation, suppressing a cell's ability to cope with cellular insult. The goal of this research is to use recent advances in nanotechnology to develop a specific nanoparticle antagonist to disrupt the mdm2:p53 interaction. Inhibiting the interaction between p53 and mdm2 allows wild-type p53 concentrations to rise to functional levels, effectively killing proliferating tumor cells. By incorporating traditional peptide inhibitors ofmdm2 with mixed monolayer protected gold cluster nanoparticles, we hope to effect mdm2 denaturation on the nanoparticle surface, increase p eptide stability, and facilitate intracellular p eptide delivery. Nanoparticle characteristics, such as size, surface chemistry and biocompatibility, may be controlled and modified for these specific applications. In the first year of the research grant, nanoparticles featuring mdm2-specific peptides have been synthesized and characterized by transmission electron microscopy, gel electrophoresis, UV-Vis absorbance, and fluorescence spectrometry. The nanoparticles are water soluble, stable for months at room temperature, and successfully inhibit the binding of mdm2 top 53. Current work is focused on optimizing peptide loading on the nanoparticle, determining changes in mdm2 conformation upon nanoparticle binding, and preparing for experiments on cultured cells.

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Insight on Heterocycles as p53‐MDM2 Protein‐Protein Interaction Inhibitors: Molecular Mechanism for p53 Activation

Basha,

Mohan

2024

ChemistrySelect

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Transcription factor p53, also known as tumor suppressor protein. Encoded by the TP53 gene, the guardian of genome p53 regulates many gene pathways. Nevertheless, the molecular mechanisms of p53 functioning have been known for a few decades, and the exact role of p53 in cancer therapy is unclear. Also, comprehensive literature on heterocycles as p53‐MDM2 protein‐protein interaction inhibitors is limited. This review covers the molecular mechanism for the p53‐MDM2 interaction and its inhibition by the heterocyclic small molecules. We hope the present comprehensive study will help to develop heterocycles as anticancer drugs that induce apoptosis in tumor cells.

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Isolation and Structure Elucidation of Chlorofusin, a Novel p53-MDM2 Antagonist from a Fusarium sp. [J. Am. Chem. Soc. 2001, 123, 554−560].

Cited by 13 publications

References 0 publications

Structural Elucidation with NMR Spectroscopy: Practical Strategies for Organic Chemists

Structural Elucidation with NMR Spectroscopy: Practical Strategies for Organic Chemists

Nanoparticle-Mediated Rescue of p53 Through Targeted Degradation of MDM2

Insight on Heterocycles as p53‐MDM2 Protein‐Protein Interaction Inhibitors: Molecular Mechanism for p53 Activation

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