1. Synthesis of a biological active β-hairpin peptide by addition of two structural motifs
- Author
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Mobarak Abu Mraheil, Dörte Brödje, Armin Geyer, Trinad Chakraborty, Matthias Lamping, Yvonne Röttger, Sabrina Fischer, Maike Gold, Richard Dodel, and Renate Frantz
- Subjects
0301 basic medicine ,Protein Conformation ,Clinical Biochemistry ,Pharmaceutical Science ,Peptide ,Microbial Sensitivity Tests ,Biochemistry ,Epitope ,Structure-Activity Relationship ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Discovery ,Escherichia coli ,Citrulline ,Structural motif ,Molecular Biology ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Bicyclic molecule ,Chemistry ,Organic Chemistry ,A protein ,Bacterial strain ,Anti-Bacterial Agents ,030104 developmental biology ,Antibiotic effect ,Molecular Medicine ,Peptides - Abstract
The idea of privileged scaffolds - that there seem to be more bioactive compounds found around some structures than others - is well established for small drug molecules, but has little significance for standalone peptide secondary structures whose adaptable shapes escape the definition of a 3D motif in the absence of a protein scaffold. Here, we joined two independent biological functions in a single highly restricted peptide to support the hypothesis that the β-hairpin shape is the common basis of two otherwise unrelated biological recognition processes. To achieve this, the hydrophobic cluster HWX4LV from the decapeptide cyclic hairpin model peptide C1-C10cyclo-CHWEGNKLVC was included in the bicyclic peptide 2. The designed β-hairpin peptide C4-C17, C8-C13bicyclo-KHQCHWECTZGRCRLVCGRSGS (2, Z=citrulline), serves, on the one hand, as a specific epitope for rheumatoid autoantibodies and, on the other hand, shows a not negligible antibiotic effect against the bacterial strain E. coli AS19.
- Published
- 2017
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