Internal mobility of cyclic RGD hexapeptides studied by 13C NMR relaxation and the model-free approach.
The internal mobility of three isomeric cyclic RGD hexapeptides designed to contain two beta-turns in defined positions, cyclo(Arg-Gly-Asp-Gly-D-Pro-Pro) (I), cyclo(Arg-Gly-Asp-D-Pro-Gly-Pro) (II) and cyclo(Arg-Gly-Asp-D-Pro-Pro-Gly) (III), have been studied by 13C NMR longitudinal and transverse relaxation experiments and measurements of steady-state heteronuclear (1H)-13C NOE enhancement with 13C at natural abundance. The data were interpreted according to the model-free formalism of Lipari and Szabo, which is usually applied to data from macromolecules or larger sized peptides with overall rotational correlation times exceeding 1 ns, to yield information about internal motions on the 10-100 ps time scale. The applicability of the model-free analysis with acceptable uncertainties to these small peptides, with overall rotational correlation times slightly below 0.3 ns, was demonstrated for this specific instance. Chemical exchange contributions to T2 from slower motions were also identified in the process. According to the order parameters obtained for its backbone alpha-carbon atoms, II has the most rigid backbone conformation on the 10-100 ps time scale, and I the most flexible. This result coincides with the results of earlier NMR-constrained conformational searches, which indicated greatest uncertainty in the structure of I and least in II.
Briand
J
J
Department of Physical and Structural Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
Kopple
K D
KD
D000818:Animals; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation
D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid