Evaluation of the Conformation-Directing Effects of Secondary Hydrogen-Bonding Interactions in Flexible Tetrapeptide Analogs

Abstract

Hydrogen bonds are involved in many interand intramolecular recognition processes, but simply counting the hydrogen bonds in a complex or folding pattern does not necessarily provide insight on stability.1 In 1990, Jorgensen and Pranata pointed out that variations among the association constants for a series of triply hydrogen bonded complexes, including the guanine-cytosine base pair, could be rationalized in terms of "secondary interactions" among the hydrogen-bonding groups.2 These secondary interactions involve electrostatic attractions or repulsions between donor (electropositive) and acceptor (electronegative) atoms forced to approach one another in the course

Partially Modified Retro-Inverso Peptides: Development, Synthesis, and Conformational Behavior

“…255,256 This result accords with DauberOsguthorpe et al's modeling study, which predicted that a six-membered hydrogen bonded ring arrangement of Ac-gAla-Ac is less stable than the extended conformation; but it contrasts with the predictions of Alemá n and Pérez and Stern et al that such an arrangement is the minimum energy conformation for Ac-gGly-Ac (section VI.C.3, above).…”

“…However, Gardner and Gellman found that their IR spectroscopic data, while consistent with the two state equilibrium depicted in Figure 13, yielded very similar equilibrium constants for the parent and PMRI depsipeptides (K ≈ 0.6, in dichloromethane). 255,256 Therefore secondary interactions do not increase the -folding propensity of 115 over that of its parent, in this case, probably because intramolecular dipoledipole repulsions result in nonplanarity of the amide groups, 255,256 a situation that cannot arise within the rigid heterocyclic systems found in nucleotide bases.…”

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

“…The most striking feature of this study indicates that the net contribution of enthalpic as well as entropie parameters in overall AG at ambient temperature is roughly comparable with those reported for other hydrogen bonded secondary structural elements mimicking various reverse turns, e.g. ß-and y-turn conformations [14,[18][19][20]23,24]. It is pertinent to note that the enthalpy-entropy internal compensation effects are the consequences of the unique complex phenomenon of flexible and/or conformationally restricted geometries of the structures and the solvent properties interacting with them.…”

The ANANKE relative energy gradient (REG) method to automate IQA analysis over configurational change

“…SIH was eagerly seized by the supramolecular community (e.g. [5][6][7][8][9][10]), which was then (and perhaps still is) in need for back-of-the-envelope guidance on complex stability beyond that given by hydrogen bonding. However, SIH is also known to fail or require further modification [5,6,[11][12][13].…”