Synthesis, and structural and biological studies of efrapeptin C analogues
Autor(en): | Jost, Micha Weigelt, Sven Huber, Thomas Majer, Zsuzsanna Greie, Joerg-Christian Altendorf, Karlheinz Sewald, Norbert |
Stichwörter: | ALPHA-AMINOISOBUTYRIC-ACID; AMINO-ACIDS; BETA-PEPTIDES; Biochemistry & Molecular Biology; Chemistry; Chemistry, Multidisciplinary; CIRCULAR-DICHROISM; CONFORMATION; ESCHERICHIA-COLI; FUNGUS TOLYPOCLADIUM-NIVEUM; MITOCHONDRIAL ATPASE; POLYPEPTIDE HELICES; RESIDUES | Erscheinungsdatum: | 2007 | Herausgeber: | WILEY-V C H VERLAG GMBH | Journal: | CHEMISTRY & BIODIVERSITY | Volumen: | 4 | Ausgabe: | 6 | Startseite: | 1170 | Seitenende: | 1182 | Zusammenfassung: | A series of analogues of efrapeptin C (1), with variations in the central tripeptide epitope (positions 6-8), were prepared by a combination of solid- and solution-phase peptide syntheses. The conformations of the modified compounds 2-6 were investigated by circular-dichroism (CD) spectroscopy to differentiate between 3(10)- and alpha-helical secondary structures. The inhibitory activities of the new compounds towards F-1-ATPase from E. coli were determined. The modified congeners 3-5 were less active by one order of magnitude compared to 1 (K-i 10 mu m), and 6 was completely inactive. Our experiments demonstrate that the flexible, central tripeptide epitope, comprising positions 6-8 in 1, is crucial for molecular recognition, even slight sequence modifications being hardly tolerated. |
ISSN: | 16121872 | DOI: | 10.1002/cbdv.200790103 |
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