Comparative conformational analyses and molecular dynamics studies of glycylglycine methyl ester and glycylglycine N-methylamide

Abstract

Amide–ester substitution and water models significantly alter conformational and solvation properties of glycine–glycine dipeptides.

Tuning the coordination properties of chiral pseudopeptide bis(2-picolyl)amine and iminodiacetamide ligands in Zn(ii) and Cu(ii) complexes

“…This suggests that the ester group is likely a good choice to be introduced in the sidechain substituents in order to promote their H-bond formation in solution, in line with their lower solvation over the matching amides in polar media, as recently demonstrated by Thakkar and Engh. 53 Still, with amides, this changes when two such groups are combined and separated by a methylene group, as in b3C′, where we note an equal stability of mer and cis-fac ML 2 isomers, with hydrogen bonding interactions still occurring in 42% of structures in the latter isomer.…”

Density Functional Studies on Secondary Amides: Role of Steric Factors in Cis/Trans Isomerization

“…In both gas and water phases ( Figure 4 and Figure 5 ), the optimized minimum energy geometries of trans isomers showed an interesting blend of peptidic features with many of the characteristics previously observed for GGMe [ 24 ]. For example, due to the absence of an amide group at the C-terminal, C 7 -forms (γ-foldings) were not observed and the geometries with unsubstituted chiral carbons showed a preference for the extended planar C 5 -form [ 38 ].…”

“…With advances in computational capabilities since the 1990s, theoretical studies on trans and cis isomers of 2°-amides and their interconversion have revealed diverse phenomena, such as: effects of pyramidalization of the amide and geometries of transition states [ 18 ]; the role of conjugation [ 19 ]; simulated solvent effects with molecular dynamics [ 20 ]; comparison of theoretically obtained rotational barrier values with experimental values [ 21 , 22 ]; and the generation of ensembles of transition state geometries [ 23 ]. Recently, we have conducted theoretical studies [ 7 , 24 ] on secondary amides using density functional methods and molecular dynamics to provide a detailed account of geometry changes during cis/trans isomerization, as well as the effects of solvent models, using glycylglycine methyl ester (GGMe, Figure 1 ) as an example. We described that cis/trans isomerization can occur via either of the two paths: one via the anti -type transition state, and one via the syn -type transition state ( Figure 2 ).…”

Non-Canonical Amino Acids as Building Blocks for Peptidomimetics: Structure, Function, and Applications

“…This modification has aroused great interest, since peptide esters have a lower propensity for intramolecular hydrogen bonding and therefore quite different molecular structure, which arises from the cyclic structure that confers proteolytic resistance, in place of the typical amide’s hydrogen bonds [ 181 ]. Thus, it is a target of investigation both computationally and experimentally, as pointed out by Thakkar and Engh and references therein [ 182 ]. Remarkable examples are the depsipeptides extracted from marine invertebrates, Didemnin B , Plitidepsin (dehydrodidemnin B) [ 183 ], and Kahalalide F [ 179 ].…”