Structure-Based Design, Synthesis and Bioactivity of a New Anti-TNFα Cyclopeptide
| Autor: | Bruce F. Milne, Gary S. Thompson, Wael E. Houssen, Laurent Trembleau, Mohannad Idress, Marcel Jaspars |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Peptidomimetic
drug design Pharmaceutical Science Peptide Pharmacology Peptides Cyclic Article Protein Structure Secondary Analytical Chemistry Protein–protein interaction lcsh:QD241-441 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine lcsh:Organic chemistry Drug Discovery Humans Physical and Theoretical Chemistry Receptor 030304 developmental biology chemistry.chemical_classification 0303 health sciences Drug discovery Tumor Necrosis Factor-alpha Organic Chemistry Biological activity cyclic peptides Small molecule 3. Good health HEK293 Cells protein–protein interaction chemistry Chemistry (miscellaneous) 030220 oncology & carcinogenesis Molecular Medicine NMR structure Tumor necrosis factor alpha |
| Zdroj: | Molecules Volume 25 Issue 4 Molecules, Vol 25, Iss 4, p 922 (2020) |
| ISSN: | 1420-3049 |
| Popis: | As opposed to small molecules, macrocyclic peptides possess a large surface area and are recognised as promising candidates to selectively treat diseases by disrupting specific protein&ndash protein interactions (PPIs). Due to the difficulty in predicting cyclopeptide conformations in solution, the de novo design of bioactive cyclopeptides remains significantly challenging. In this study, we used the combination of conformational analyses and molecular docking studies to design a new cyclopeptide inhibitor of the interaction between the human tumour necrosis factor alpha (TNF&alpha ) and its receptor TNFR-1. This interaction is a key in mediating the inflammatory response to tissue injury and infection in humans, and it is also an important causative factor of rheumatoid arthritis, psoriasis and inflammatory bowel disease. The solution state NMR structure of the cyclopeptide was determined, which helped to deduce its mode of interaction with TNF&alpha TNF&alpha sensor cells were used to evaluate the biological activity of the peptide. |
| Databáze: | OpenAIRE |
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