Conformational mobility in cyclic oligopeptides.
Analysis of two isomeric cyclic hexapeptides of composition (Asp, Arg, Gly2, Pro, D-Pro) by a nuclear Overhauser effect constrained distance geometry conformation search yielded a narrowly defined backbone conformation for one and considerable ambiguity about the conformation in part of the other. Preliminary 13C relaxation studies of these peptides suggest that it is possible that this difference may correspond to a physical difference in internal mobility. In connection with this observation, other experimental evidence bearing on the backbone conformational mobility of cyclic oligopeptides with 4-10 residues, frequently considered to have well-defined backbones, is reviewed. Conformational heterogeneity involving rotation of a peptide bond plane relative to the overall ring plane is identified as a common phenomenon. Nuclear magnetic resonance line-shape studies at temperatures down to 200 K can detect backbone motions with activation free energy barriers down to about 10 kcal/mole, but conformational exchange with lower barriers, though detectable in other ways, will not be obvious from nmr spectra alone.
Kopple
K D
KD
Department of Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406.
Bean
J W
JW
Bhandary
K K
KK
Briand
J
J
D'Ambrosio
C A
CA
Peishoff
C E
CE
D000595:Amino Acid Sequence; D001127:Arginine Vasopressin / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D013004:Somatostatin / Q000031:analogs & derivatives / Q000737:chemistry; D013329:Structure-Activity Relationship; D013696:Temperature
D010456:Peptides, Cyclic; D001127:Arginine Vasopressin; D013004:Somatostatin