Synthesis, and structural and biological studies of efrapeptin C analogues.
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 microM), 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.
Jost
Micha
M
Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, Bielefeld, Germany.
Weigelt
Sven
S
Huber
Thomas
T
Majer
Zsuzsanna
Z
Greie
Jörg-Christian
JC
Altendorf
Karlheinz
K
Sewald
Norbert
N
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects; D008958:Models, Molecular; D054848:Peptaibols; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction
D000900:Anti-Bacterial Agents; D054848:Peptaibols; D010455:Peptides; C471725:efrapeptin C