The three-dimensional solution structure of a constrained peptidomimetic in water and in chloroform. Observation of solvent induced hydrophobic cluster.
A large number of protein-protein interactions involved turn or loop regions. The excised linear peptides from these regions reveal complex conformational averaging. To circumvent this motional averaging and to stabilize the beta-turn conformation, extensive effort has been devoted to the design of constrained peptidomimetics. Here, we report the three-dimensional solution structure of a 12-membered cyclic peptidomimetic. The structures were calculated from NMR studies performed in chloroform and in water at 263 and 278K, respectively. This 12-membered cyclic scaffolding is part of a program to design and to construct conformationally stable beta-turn peptidomimetics. The impact of the surrounding environment on the conformation of this constrained peptidomimetic is discussed. The general structural features of the cyclic mimetic are retained in both environments; however, the formation of a hydrophobic patch in the aqueous solvent is evident.
Lee
M S
MS
Molecumetics, Bellevue, WA 98005.
Gardner
B
B
Kahn
M
M
Nakanishi
H
H
D000595:Amino Acid Sequence; D002725:Chloroform; D004745:Enkephalins / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D012996:Solutions; D014867:Water
D004745:Enkephalins; D010456:Peptides, Cyclic; D012996:Solutions; D014867:Water; D002725:Chloroform