Effects of amino acids and chirality for molecular folding of desoxazoline-ascidiacyclamide derivatives: X-ray crystal structures of four cyclic octapeptides including unusual amino acids, cyclo(-Ile-aThr-D-Val-Thz-)(2), cyclo(-Ala-aThr-D-Val-Thz-Ile-aThr-D-Val-Thz-), cyclo(-Val-aThr-D-Val-Thz-Ile-aThr-D-Val-Thz-), and cyclo(-Ile-aThr-Val-Thz-Ile-aThr-D-Val-Thz-).
Desoxazoline derivative of ascidiacyclamide (1), cyclo(-L-Ile-L-allo-threonine-D-Val-thiazole-)(2), was modified to disturb the C(2)-symmetry. An Ile(1) residue of 1 was replaced for Ala (2) or Val (3), and the D-Val(3) residue was replaced for Val (4). The crystal structures of 1-4 were analyzed by x-ray diffraction methods. The molecules of all compounds were folded and this type of structure was not observed in x-ray structures of ascidiacyclamide derivatives so far except for patellamide D. The folding patterns of 1-4 were similar to each other and resembled that of patellamide. The asymmetric modifications at position 1 caused the conformational changes at local area, and these were related with the peptide-peptide and peptide-solvent interactions. Despite the diverse backbone conformation by the epimeric modification at position 3, the entire molecule of 4 was folded. These results mean that (1) the desoxazoline-ascidiacyclamides favored the folded structures and (2) the modifications of the side chain size at position 1 and the chirality at position 3 brought the local conformational changes to derivatives, suggesting that (3) the lack of the oxazoline block leads to conformational flexibility of 1-4, which accepts the conformational change with no drastic change on the entire structure.
Asano
A
A
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Doi
M
M
Kobayashi
K
K
Arimoto
M
M
Ishida
T
T
Katsuya
Y
Y
Mezaki
Y
Y
Hasegawa
H
H
Nakai
M
M
Sasaki
M
M
Taniguchi
T
T
Terashima
A
A
D000596:Amino Acids / Q000737:chemistry; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding
D000596:Amino Acids; D010456:Peptides, Cyclic; C059972:patellamide D; C075813:ascidiacyclamide