[Conformational analysis of biologically active thyroliberin analogs by two-dimensional NMR spectroscopy].
Preferable conformations of thyrotropin-releasing hormone (TRH, Glp-His-Pro-NH2) and its analogues Glp-Glu(R)-Pro-NH2 (R = NHCH(CH3)CH2Ar), Glp-Gln-Abu-NH2, Dho-Gln-Abu-NH2 in DMSO solution are determined using two-dimensional 1H NMR spectroscopy (delta-J-correlated, COSY and NOESY). Torsion angles psi i and chi i for every amino acid were calculated on the basis of the spin-spin coupling constants 3JNH-C alpha H and 3JC alpha H-C beta H values. The NOESY data were used for selecting the peptide conformations realized in solution. Distances between protons interacting by the dipole mechanism (d-contacts) were calculated using NOE values. These experiments allow one to estimate the torsion angles psi (between C alpha H-CO). TRH has an intramolecular H-bond between NH2-protons and His carbonyl with the torsion angles omega 3 = 180 degrees and psi 3 = 0 degrees. It is formation of this H-bond that apparently promotes the domination of the trans configuration of the His-Pro peptide bond. An intramolecular NH2-C alpha CO (Glp) H-bonding is revealed in other investigated compounds. It is known that a similar conformation of the TRH is realized in the course of its interaction with receptor.
Gorbatiuk
V Ia
VIa
Shapiro
Iu E
IuE
Mazurov
A A
AA
Zhuravlev
V G
VG
Andronati
S A
SA
Korotenko
T I
TI
Romanovskiĭ
P Ia
PIa
D000595:Amino Acid Sequence; D005583:Fourier Analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D011487:Protein Conformation; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism*
D013973:Thyrotropin-Releasing Hormone
Konformatsionnyĭ analiz biologicheski aktivnykh analogov tiroliberina metodami dvumernoĭ spektroskopii IaMR.