Salt bridges in model peptides

Abstract

A group of synthetic peptides including Boc-Lys-Phe-X-Y, X = Ala (I, III) or Thr (II), Y = Pro (I, II) or Ala (III) was studied by means of 1H NMR spectroscopy and theoretical conformational analysis. Compound I in DMSO shows two conformers with the trans- and cis-configuration of the peptide bond Ala-Pro. The salt bridge between the Lys ε-amino group and the C-terminal carboxyl is featured by magnetic nonequivalence of the Lys CεH2 protons. The space structure of I and II was found to possess a salt bridge fixed by an unusual turn in the chain formed by the Lys side chain and the C-terminal dipeptide with the trans-peptide bond X-Pro. Since a stable ionic bond in III and in the cis-conformer of I has not been observed, its contribution to stabilization of the space structure of the peptides in DMSO appears rather small.

Conformational analysis of [Cpp1, Sar7, Arg8] vasopressin by 1H‐NMR spectroscopy and molecular mechanics calculations

“…A NOE observed between the Cys6C"H and Sar7N-CH, resonances of the main isomer (the cross-peak indicated as C6-Sc7 in Fig. 1, part B) is characteristic of the trans peptide bond (4, 19,26), while the NOF; between the Cys6 and Sar7C"H resonances of the minor isomer (the cross-peak indicated as mC6-mSc' in Fig. I , part B) can only be observed given the cis-configuration of the Cys6-Sar7 peptide bond (26).…”

“…The calculations were first performed using the ECEPP/2 potential function (28) with standard rigidvalence geometry. To simulate the effect of a polar environment the dielectric constant E = 47, corresponding to DMSO, was used in calculations with ECEPP/2 potentials (26), while in calculations with AMBER force field the dielectric constant was distance-dependent ( E = rV). 29.…”

“…The low-energy conformations obtained in the ECEPP/2 approximation were next energy-minimized using the AMBER molecular mechanics force field (1 2), which implies relaxation of all degrees of freedom, including the valence geometry, during the energy minimization. To simulate the effect of a polar environment the dielectric constant E = 47, corresponding to DMSO, was used in calculations with ECEPP/2 potentials (26), while in calculations with AMBER force field the dielectric constant was distance-dependent ( E = rV). The calculations in ECEPP/2 potential system were performed using an all-atom scheme, while those in AMBER potential system utilized the united-atom scheme (i.e.…”

“…1, part B)is characteristic of the trans peptide bond (4,19,26), while the NOF; between the Cys6 and Sar7C"H resonances of the minor isomer (the cross-peak indicated as mC6-mSc' inFig. NOE connections of the c" H resonances of the Cys6 residue prove the cis-trans isomerization of the Cys6-Sar7 peptide bond.…”

“…double set of resonances, most clearly distinguished for spin systems of the C-terminal tripeptide, indicates the presence of two isomers of [Cpp', Sar7] AVP in DMSO solution. I , part B)can only be observed given the cis-configuration of the Cys6-Sar7 peptide bond(26). 2D ROESY spectrum of [Cpp', Sar'IAVP in DMSO at 308 K, the mixing time ( T~) being 198ms.…”