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

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.