13C NMR relaxation studies of molecular motion in peptide fragments from human transthyretin.
Natural-abundance 13C T1 and NOE measurements have been made for backbone and side-chain sites in peptide fragments of transthyretin (TTR 10-20, TTR 105-115, and TTR 105-115Met111) at 13C Larmor frequencies of 125 and 75 MHz. These peptides have previously been implicated in the formation of amyloid fibrils. The data were systematically assessed for their consistency with theoretical relaxation parameters derived from models of molecular motion. It was shown that of four models, ranging from simple isotropic motion to one defining internal wobbling of the 13C-1H vector, the "model-free approach" (Lipari and Szabo, J. Am. Chem. Soc. 104, 4546, 1982) was best able to predict the experimental data. These peptides exhibited overall correlation times close to 1 ns. Internal motions with effective correlation times of approximately 0.08 ns were observed for backbone carbon sites, and side-chain carbons exhibited more rapid and less ordered motions. No indication of retarded motion due to the presence of small peptide aggregates was detected, in agreement with reports of the rapid incorporation of these species into amyloid fibrils.
Jarvis
J A
JA
School of Pharmaceutical Chemistry, Victorian College of Pharmacy, Monash University, Parkville, Australia.
Craik
D J
DJ
D000595:Amino Acid Sequence; D002247:Carbon Isotopes; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry*; D011228:Prealbumin / Q000737:chemistry*; D011487:Protein Conformation
D002247:Carbon Isotopes; D010446:Peptide Fragments; D011228:Prealbumin