Synthesis of a biological active β-hairpin peptide by addition of two structural motifs. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Fischer, Sabrina; Lamping, Matthias; Gold, Maike; Röttger, Yvonne; Brödje, Dörte; Dodel, Richard; Frantz, Renate; Mraheil, Mobarak Abu; Chakraborty, Trinad; Geyer, Armin
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 2(2017)
• Page Start: 603
• Page End: 608
• Publication Date: 2017-01-15
• Subjects: Peptides -- Disulfides -- β-Hairpin -- NMR spectroscopy -- Filaggrin; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.11.022
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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 HWX4 LV from the decapeptide cyclic hairpin model peptide C 1 -C 10 cyclo- CHW EGNKLV C was included in the bicyclic peptide2 . The designed β-hairpin peptide C 4 -C 17, C 8 -C 13 bicyclo- KHQCHW ECTZGRCRLV CGRSGS (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.