Conformational study of some component peptides of pentagastrin

Abstract

Phe-NH, have been studied in aqueous and dimethyl sulphoxide solutions. From an analysis of the 1H spectra of the Asp and Phe C(a)H-C(P)H, side-chains the vicinal coupling constants were obtained and used to calculate the rotational populations. There are no significant differences in the Phe side-chain rotamer populations between the tripeptide Met-Asp-Phe-NH, and gastrin pentapeptide PAla-Trp-Met-Asp-Phe-N H, , but the Asp residue shows some small changes.The presence of only small ring-current shielding contributions to the Phe aromatic protons from the aromatic ring in Trp can be taken to indicate that the aromatic rings are well separated ( > 5 8 ) in the most populated conformers of gastrin pentapeptide in aqueous solution.For dimethyl sulphoxide solutions, NH doublets could be observed for the peptides studied; the large values of the vicinal JNa coupling constants for Met, Asp, and Phe in the tetrapeptide Trp-Met-Asp-Phe-NH, are shown to be consistent with the most populated conformations, having a C $ angle of ca. -95". from considerations of potential energy diagrams and the Bystrov-modified Karplus curve which relates dihedral angles to vicinal coupling constants.

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

“…No evidence for other than a random-coil configuration for TRF could be found in the spectrum. Similar findings have been reported for other small linear peptides such as pentagastrin [9] and luteinizing hormone releasing hormone [ 10]. It would appear that for these peptides where the active groups are in close proximity to each other, the hormone structure can possibly organise itself into its bound conformation during the actual binding process to the receptor.…”

“…contains the rotamer fractional populations calculated by assuming that a mixture of rotamers is present. Thus it is seen that TRF and ~GluHisOCH3 do have some conformational differences mainly for the populations of rotamers I and 1I: this could simply be a reflection of the larger size of the group R2 in TRF (in~"GluHisOCHa, R2 = OCH3 : in TRF, Rz = ProNH2) which is known to increase the population of the rotamer with the bulky substituent gauche to H A and H B (rotamer 1I) [9]. Some workers [3] have considered the possibility that the His side chain in TRF is in a fixed conformation resulting from a hydrogen bonding interaction between an imidazole nitrogen and the His peptide NH proton.…”

Assignment and conformation of neurotensin in aqueous solution by 1H NMR

“…A similar titration behaviour was found in amide signals of random coil tetrapeptides containing Glu (23). Coupling constants within that range can be explained as averaged random coil conformations (25,28). It is to be noted that a similar situation has been found in the 15-19 region of the 1-19 S-peptide in random coil conditions (6), where an upfield titration shift has been detected for the a i d e signal of Thr 17 which is 2 residues away from the terminal carboxylate of Ala 19 (to be published).…”

Targets of Drug Action

“…We were able to show that most of their motion in solution was due to a tumbling of the whole molecule rather than to rotation around bonds. We also showed that such small peptides as TRF, LHRF, and gastrin tetrapeptide were random coils without any evidence of tertiary structure (21). In the normal state, with intact SS bonds, the structures of vasopressin and oxytocin resembled each other, with restricted motional possibilities in the ring, and showing no evidence of either hydrogen bonding or the tail peptide being folded over the ring, as had previously been suggested.…”