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Synthesis, and Structural and Biological Studies of Efrapeptin C Analogues
Author(s) -
Jost Micha,
Weigelt Sven,
Huber Thomas,
Majer Zsuzsanna,
Greie JörgChristian,
Altendorf Karlheinz,
Sewald Norbert
Publication year - 2007
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200790103
Subject(s) - tripeptide , chemistry , circular dichroism , epitope , stereochemistry , peptide , protein secondary structure , sequence (biology) , angstrom , crystallography , biochemistry , antibody , immunology , biology
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 α ‐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 μ 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.