Synthesis of a biological active β-hairpin peptide by addition of two structural motifs

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• 作者：Sabrina Fischer^a ; Matthias Lamping^a ; Maike Gold^b ; Yvonne Rö ; ttger^b ; Dö ; rte Brö ; dje^c ; Richard Dodel^b ; Renate Frantz^d ; Mobarak Abu Mraheil^d ; Trinad Chakraborty^d ; Armin Geyer^a ; ^{geyer@staff.uni-marburg.de}
• 关键词：Peptides ; Disulfides ; β-Hairpin ; NMR spectroscopy ; Filaggrin
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：25
• 期：2
• 页码：603-608
• 全文大小：1382 K
• 卷排序：25

文摘

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.