Energetic contribution to both acidity and conformational stability in peptide models

Abstract

The acidity of N-acyl amino acids is dependent upon the rotameric state of the amide bond. In this work we systematically investigated the acidity difference of the rotamers (Delta pK(a)) in the frames of various acetylated amino acids. Our results indicated a mutual interaction of two carbonyl groups of an attractive type. We observed conservative Delta pK(a)s for acyclic amino acids (2.2-3.0 kJ mol(-1)), whereas in the case of alicyclic amino acids, the experimental values revealed a strong dependency on the structural context (1.5-4.4 kJ mol(-1)). In homologous amino acids (alpha-, beta-, gamma-, etc.), the strength of the attraction decays in an exponential fashion. Furthermore, the interaction can accumulate through a chain of amide bonds in a cascade fashion, as demonstrated by an Ac-Pro-Pro dipeptide. As a result, we demonstrate that Delta pK(a) is an experimental parameter to estimate increments in the carbonyl-carbonyl alignment, as determined by the amino acid or peptidyl context. This parameter is also important in understanding the roles of amino acids in both protein folding and translation in biological systems as well as their evolutionary appearance in the genetic code.DFG, EXC 314, Unifying Concepts in Catalysi

Exploring hydrophobicity limits of polyproline helix with oligomeric octahydroindole‐2‐carboxylic acid

“…Conversely, the P II helix is not stabilized by macrocyclic hydrogen bonds (13 atoms forming a ring in an α‐helix), but it results from short‐distant interactions between the neighboring residues (5 atoms in a ring; see Figure for illustration) . The latter may be weak, and the previously found estimates for the interaction energies are around 3 to 3.5 kJ mol −1 per residue for proline and ≤5 kJ mol −1 per residue for Oic with locked exo ‐pucker, with ≤2 kJ mol −1 per residue stability enhancement via the cascade effect . At the same time, this interaction is less dependent on environment conditions such as temperature, or presence of denaturing additives due to the favorability of the intramolecular 5‐membered ring formation.…”

“…This fact is attributed to increasing strength of the stabilizing hydrogen bonds in nonpolar media . Conversely, the P II helix is not stabilized by macrocyclic hydrogen bonds (13 atoms forming a ring in an α‐helix), but it results from short‐distant interactions between the neighboring residues (5 atoms in a ring; see Figure for illustration) . The latter may be weak, and the previously found estimates for the interaction energies are around 3 to 3.5 kJ mol −1 per residue for proline and ≤5 kJ mol −1 per residue for Oic with locked exo ‐pucker, with ≤2 kJ mol −1 per residue stability enhancement via the cascade effect .…”

“…1 H exchange spectroscopy NMR analysis was performed for a 20mM sample in deuterium oxide at 280 K and 700‐MHz frequency. The exchange data were obtained in 1 H z‐cross‐relaxation experiments assisted with z‐gradients, and these spectra were processed as described . The examined mixing times were 100, 50, 30, and 25 milliseconds for exchange and 3 milliseconds for referencing.…”

“…In contrast to most conventional peptide structures, the local order in the P II helix is a product of generic interactions between polar amide groups. The latter may be quite complex, as these may be described in terms of n→π* donation, dipole‐dipole interaction, carbonyl‐carbonyl interaction, and the cascade effect . The geometric simplicity of this secondary structure (1 turn = 3.0 residues ≈ 9.0 Å) is also well appreciated and has been used as a molecular ruler for spectroscopic distance measurements and for a variety of other studies based on molecular distance control …”

Geometric Isomerism of an Acetamidino Derivative Determined by NMR Investigations

“…Once we stated the coexistence of a E / Z mixture after solvent extraction of 5 a , we tried to investigate the influence of several factors, such as solvent polarity and temperature on the rotamer equilibrium, as already described for other amidines ,…”