Thermodynamic characterizations of an intramolecularly hydrogen bonded C₅‐structure across proteinogenic residue

Abstract

Thermodynamic investigations of a smallest possible intramolecularly hydrogen bonded C 5 -structure, across a Thr residue, in model peptides Boc-Xxx-Thr-NH2 (Xxx = Ile, 1 or Leu, 2), indicated unusual thermal stability of the structure in non-polar medium. An analysis of van't Hoff plots, constructed from variable temperature 1 H NMR data, yielded the thermodynamic parameters of a hydrogen bonded five-membered ring. The non-significance of the spatial organizations of the preceding C s H :i bearing hydrophobic proteinogenic residue on the thermal stability of the Cs-structure has been observed. The results revealed that the contribution of this element of secondary structure is quantifiable and the stability appeared to be roughly comparable to other intramolecularly hydrogen bonded reverse turn structures frequently observed in poly peptides and proteins.

Self-Association Behavior of aNovelNonproteinogenic β-Strand-Mimicin an Organic Solvent

“…So far, our results establish that the newly identified β-strands- mimic experiences self-association primarily via the amide–amide interaction and the Ar···Ar interactions seem to impart incremental stability in a nonpolar organic solvent. The fact that both amide-NHs not only showed concentration and temperature dependences of the 1 H NMR chemical shift in CDCl 3 but also significantly large Δδ/Δ T values at high concentrations as a result provides evidence for the existence of self-associated molecular species equilibrating between H-bonded and non-H-bonded states. − Because the formation of dimers and larger aggregates is facilitated via H-bonding, the next step was to evaluate their relative contributions toward stabilization by elucidating thermodynamic parameters from variable temperature 1 H NMR data of amide-NHs in CDCl 3 . As depicted in Figure , considering a two-state process, i.e., non-H-bonded ( n ) and H-bonded ( b ) dimeric states, we determined the equilibrium constant K eq at several temperatures according to the equation K eq = (δ obs – δ n )/(δ b – δ obs ) where δ n and δ b represent the limiting chemical-shift values for non-H-bonded and fully-H-bonded conformers, respectively .…”

“…The limiting chemical-shift values corresponding to non-H-bonded and fully-H-bonded states of the model compound NMA were integrated in the equation. The temperature dependences of K eq were used for constructing van’t Hoff plots for the H-bonded amide-NHs using the van’t Hoff equation [ln K eq = (−Δ H / R )·1/ T + (Δ S / R )]. ,,,, As shown in Figure , the linearity of van’t Hoff plots, i.e., ln K eq vs 1/ T (K –1 ), provides evidence that the enthalpic (Δ H ) and entropic (Δ S ) differences between H-bonded and non-H-bonded states are temperature independent, i.e., Δ C p ≈ 0. The deduced thermodynamic parameters, summarized in Table , tend to suggest that at high concentrations, when solute–solute interactions predominate, the H-bonded self-associated structures involving γ-Abz NH and methylamide NH are enthalpically favorable by ∼1.4 and 1.8 kcal/mol and entropically disfavored by ∼6.3 and 6.0 eu, respectively.…”

Isostructural unbranched alkyl‐chains as tools for stabilizing β‐turn structure

“…To provide deeper insights on structural stability, we assessed energetic contributions by determining thermodynamic parameters, that is, enthalpic (Δ H °) and entropic (Δ S °) involvements, of 1 and compared with that of 2 . Gellman and coworkers have previously demonstrated the significance of reduced temperature‐coefficients of internally hydrogen‐bonded amide‐NHs, that is, dδ/d T values, determined from variable‐temperature 1 H NMR experiment in the non‐polar chlorocarbon solvents, for extracting relevant thermodynamic information via van't Hoff analysis …”

“…Considering the two‐state process, that is, hydrogen‐bonded ( b ) and non‐hydrogen‐bonded ( n ) states, we determined the equilibrium constant K eq at several temperatures according to the equation K eq = (δ obs − δ n )/(δ b − δ obs ), where δ n and δ b represent the limiting chemical‐shift values for non‐hydrogen‐bonded and fully hydrogen‐bonded conformers, respectively . As illustrated in Figure , the temperature dependence of K eq was utilized for constructing a van't Hoff plot for the hydrogen‐bonded amide‐NHs using the van't Hoff equation [ln K eq = (–Δ H °/R)·1/ T + (Δ S °/R)] . In the light of 1 H NMR derived thermodynamic parameters, it appears that the hydrogen‐bonded β‐turn conformations in both 1 and 2 are enthalpically more favorable by ∼1.7 and 2.0 kcal/mol and entropically disfavored by ∼4.8 and 5.5 eu.…”

Characterization of a novel type VII β‐turn conformation for a bio‐active tetrapeptide rigin

“…While considering the possibilities of various secondary structural elements, i.e. C 5 ‐structure [28,29], γ‐turn [30,31] and different types of β‐turn structures [32–37] that could be accessible to this short linear peptide, only 92 structures could be grouped into three major families A, B and C, containing 34, 22 and 36 structures, respectively. The structures having an rmsd < 0.7 Å for backbone nonhydrogen atoms, including the five‐membered pyrrolidine ring of the Pro residue, were considered part of one family as shown in their superimpositions depicted in Fig.…”