Solution and solid state structure of an aib-containing cyclodecapeptide inhibiting the cholate uptake in hepatocytes.
The conformational analysis of synthetic cyclodecapeptide c(Pro-Phe-phe-Aib-Leu)2 related to the cyclolinopeptide A, in the solid state and solution, has been carried out by x-ray diffraction and nmr spectroscopy. The structure of the monoclinic form obtained from methanol [a = 11.351 (5) A, b = 27.455 (2) A, c = 12.716 (8) A, beta = 99.65 (3) degrees; space group P2(1); Z = 2] shows the presence of six intramolecular NH...CO hydrogen bonds, with formation of four turns (three of type I and one of type III) and two C16 ring structures. All peptide units are trans. The solution structure, as found by nmr, indicates that, at room temperature, the peptide is conformationally homogeneous; the structure determined is perfectly symmetrical and topologically similar to that found in the solid state. The cyclodecapeptide exhibits similar biological activity to cyclolinopeptide A.
Rossi
F
F
Dipartimento di Chimica, Università di Napoli Federico II, Italy.
Saviano
M
M
Di Talia
P
P
Di Blasio
B
B
Pedone
C
C
Zanotti
G
G
Mosca
M
M
Saviano
G
G
Tancredi
T
T
Ziegler
K
K
Benedetti
E
E
D000818:Animals; D002478:Cells, Cultured; D002725:Chloroform / Q000494:pharmacology; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D013696:Temperature
D002793:Cholic Acids; D010456:Peptides, Cyclic; C055018:cyclolinopeptide A; D002725:Chloroform; D019826:Cholic Acid