Proton NMR studies on thyrotropin releasing factor

1 H nuclear magnetic resonance studies of thyrotropin releasing factor (TRF)

“…Grant and co-workers [ 1 ] noted anomalous pK values for the imidazole protonation in TRF and interpreted this in terms of hydrogen bonding structures involving the nitrogen of the imidazole ring and the a-NH of the histidine to form a six-membered ring. Fermandjian et al [2], from proton NMR measurements in DMSO-d6 solution, have proposed a structure with this hydrogen bond and a further hydrogen bond between the His peptide carbonyl oxygen and the trans proton of the Pro amide group. Other workers [3], on the basis of semi-empirical energy calculations and the pH dependence of the proline 6-protons have proposed that this second hydrogen bond acceptor is the carbonyl oxygen of the pyroglutamyl* residue (rather than that of the histidine) making a/3-turn in TRF.…”

13C-nuclear magnetic resonance study of [85% 13C-enriched proline]thyrotropin releasing factor: 13C-13C vicinal coupling constants and conformation of the proline residue.

“…Conformational studies, both theoretical and experimental, are also numerous. The choices of conformation permitted by this short peptide molecule, which contains a proline residue known to introduce significant steric hindrance, are reflected in the various models proposed (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

On the conformation of thyrotropin releasing hormone

“…After comparisons between the pKa values and biological potencies of TRH and analogs of TRH Grant et al [6] suggested a preferred conformation of TRH having a hydrogen bond between the imidazol nN and the histidyl aN-H. From results of NMR studies Fermandjian et al [7] proposed a similar conformation for the His moiety. Burgess et al [11 ] more recently suggested a somewhat different conformation of TRH from results obtained on conformational energy calculations of TRH and several of its analogs.…”

“…If the inactivity of the Me-esters, 2 and 4, reflect the inability of these analogs to form the seven membered ring between the C-terminal N-H and the previous peptide bond [7,11 ] then this requirement is extremely important for activity. The modification of TRH to its corresponding Me-ester will greatly diminishes its hormonal activity [3][4][5].…”

“…Another approach to the structure -function problem of TRH is to define the shape of the molecule and the relationship between conformation and biological activity. Recently several papers have appeared which are concerned with conformations of TRH [6][7][8][9][10].…”