Estersubstitutionen in α‐helicalen Coiled‐Coil‐Peptiden: Effekt der Eliminierung von Wasserstoffbrücken auf die Struktur von Proteinen

A High‐Resolution Structure that Provides Insight into Coiled‐Coil Thiodepsipeptide Dynamic Chemistry

“…GnHCl‐dependent denaturation experiments have shown that the coiled‐coil structure of 1 t is less stable than that of 1 by 1.1 kcal mol −1 ,14 namely implying about 0.4 kcal mol −1 structure destabilization for each thioester bond. The relatively minor destabilizing effect is similar to that observed earlier for removing a solvent exposed hydrogen bond,7 and can be explained by water molecules solvation of the sulfur (and oxygen) atoms, which reduces repulsion between them and the K14 carbonyl oxygen lone pair 7…”

A High‐Resolution Structure that Provides Insight into Coiled‐Coil Thiodepsipeptide Dynamic Chemistry

“…GnHCl-dependent denaturation experiments have shown that the coiled-coil structure of 1 t is less stable than that of 1 by 1.1 kcal mol À1 , [14] namely implying about 0.4 kcal mol À1 structure destabilization for each thioester bond. The relatively minor destabilizing effect is similar to that observed earlier for removing a solvent exposed hydrogen bond, [7] and can be explained by water molecules solvation of the sulfur (and oxygen) atoms, which reduces repulsion between them and the K14 carbonyl oxygen lone pair. [7] Figure 3 b shows that the thioester bond is solventexposed, but it is also engulfed by the side-chains of residues K15, X21 (X = aryl-modified Lys; Figure 1), and E22 of the same chain, and E20 from the opposing helix.…”

“…The relatively minor destabilizing effect is similar to that observed earlier for removing a solvent exposed hydrogen bond, [7] and can be explained by water molecules solvation of the sulfur (and oxygen) atoms, which reduces repulsion between them and the K14 carbonyl oxygen lone pair. [7] Figure 3 b shows that the thioester bond is solventexposed, but it is also engulfed by the side-chains of residues K15, X21 (X = aryl-modified Lys; Figure 1), and E22 of the same chain, and E20 from the opposing helix. The regular Figure S6.…”

“…New structures are obtained, and new functions gained, by attachment of amino acids with non-native side-chains, [1,2] modified backbones such as b-and g-amino acids, [3][4][5] or peptide bond analogues such as peptoids, esters, and thioesters. [6][7][8][9] Backbone modification with longer and flexible amino acids allows expansion of the conformational space occupied by proteins, while introduction of ester (depsipeptide) and thioester (thiodepsipeptide) bonds enhances their reactivity towards hydrolysis and other nucleophilic attacks. The durability of thioester bonds in neutral aqueous solutions and their reactivity in thiol-thioester exchange reactions make them a relevant choice for performing dynamic chemistry in water.…”