التفاصيل البيبلوغرافية
| العنوان: |
Identifying the Cellular Target of Cordyheptapeptide A and Synthetic Derivatives |
| المؤلفون: |
Victoria G. Klein (9225489), Walter M. Bray (132474), Hao-Yuan Wang (1490710), Quinn Edmondson (6068012), Joshua Schwochert (1670326), Satoshi Ono (381142), Matthew R. Naylor (2823329), Alexandra C. Turmon (6068015), Justin H. Faris (11113126), Okimasa Okada (6681620), Jack Taunton (67759), R. Scott Lokey (133725) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Genetics, Pharmacology, Biotechnology, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, side chain, NCI -60 cell line panel, protein synthesis inhibitor, membrane permeability, cordyheptapeptide, Synthetic Derivatives Cordyheptapeptide, intracellular disease targets, backbone amide N, cytotoxicity profile, eukaryotic translation elongation f., lipophilic compounds, Cellular Target, bioactivity, backbone-modified derivatives, eEF 1A, intramolecular hydrogen bond, cancer cell lines, solid-phase synthesis, microscopy-based cytological assay, physicochemical properties, lipophilic cyclic peptide, methylated cyclic heptapeptide, cyclic peptide |
| الوصف: |
Cordyheptapeptide A is a lipophilic cyclic peptide from the prized Cordyceps fungal genus that shows potent cytotoxicity in multiple cancer cell lines. To better understand the bioactivity and physicochemical properties of cordyheptapeptide A with the ultimate goal of identifying its cellular target, we developed a solid-phase synthesis of this multiply N -methylated cyclic heptapeptide which enabled rapid access to both side chain- and backbone-modified derivatives. Removal of one of the backbone amide N -methyl (N-Me) groups maintained bioactivity, while membrane permeability was also preserved due to the formation of a new intramolecular hydrogen bond in a low dielectric solvent. Based on its cytotoxicity profile in the NCI-60 cell line panel, as well as its phenotype in a microscopy-based cytological assay, we hypothesized that cordyheptapeptide was acting on cells as a protein synthesis inhibitor. Further studies revealed the molecular target of cordyheptapeptide A to be the eukaryotic translation elongation factor 1A (eEF1A), a target shared by other lipophilic cyclic peptide natural products. This work offers a strategy to study and improve cyclic peptide natural products while highlighting the ability of these lipophilic compounds to effectively inhibit intracellular disease targets. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/journal_contribution/Identifying_the_Cellular_Target_of_a_Cordyheptapeptide_A_and_Synthetic_Derivatives/14959642 |
| DOI: |
10.1021/acschembio.1c00094.s001 |
| الاتاحة: |
https://doi.org/10.1021/acschembio.1c00094.s001 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.4457EFFD |
| قاعدة البيانات: |
BASE |