Elusive π-helical peptide foldamers spotted by chiroptical studies

Silvio, Sergio Di; Bologna, Fabio; Milli, Lorenzo; Giuri, Demetra; Zanna, Nicola; Castellucci, Nicola; Monari, Magda; Calvaresi, Matteo; Górecki, Marcin; Angelici, Gaetano; Tomasini, Claudia

doi:10.1039/c9ob02313e

Cited by 6 publications

(9 citation statements)

References 67 publications

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“…The p i values correspond to the number of times the molecular dynamics trajectory “visits” a given bin. The whole set of G values was normalized [ 68 , 69 ] in such a way that the lowest value (i.e., the most populated bin) corresponds to 1.…”

Section: Methodsmentioning

confidence: 99%

Dissecting the Supramolecular Dispersion of Fullerenes by Proteins/Peptides: Amino Acid Ranking and Driving Forces for Binding to C60

Marforio

Calza

Mattioli

et al. 2021

IJMS

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Molecular dynamics simulations were used to quantitatively investigate the interactions between the twenty proteinogenic amino acids and C60. The conserved amino acid backbone gave a constant energetic interaction ~5.4 kcal mol−1, while the contribution to the binding due to the amino acid side chains was found to be up to ~5 kcal mol−1 for tryptophan but lower, to a point where it was slightly destabilizing, for glutamic acid. The effects of the interplay between van der Waals, hydrophobic, and polar solvation interactions on the various aspects of the binding of the amino acids, which were grouped as aromatic, charged, polar and hydrophobic, are discussed. Although π–π interactions were dominant, surfactant-like and hydrophobic effects were also observed. In the molecular dynamics simulations, the interacting residues displayed a tendency to visit configurations (i.e., regions of the Ramachandran plot) that were absent when C60 was not present. The amino acid backbone assumed a “tepee-like” geometrical structure to maximize interactions with the fullerene cage. Well-defined conformations of the most interactive amino acids (Trp, Arg, Met) side chains were identified upon C60 binding.

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Section: Methodsmentioning

confidence: 99%

Dissecting the Supramolecular Dispersion of Fullerenes by Proteins/Peptides: Amino Acid Ranking and Driving Forces for Binding to C60

Marforio

Calza

Mattioli

et al. 2021

IJMS

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“…The natural transition orbital (NTO) method can provide a better qualitative description of the excited states than the commonly listed MO-pair contributions. 36 The orbital description of the left-handed helix giving rise to the respective band is shown in Figure 11. The transitions responsible for the two bands in the ECD spectra stem from delocalized π−π* transitions.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Solvent-Dependent Folding Behavior of a Helix-Forming Aryl-Triazole Foldamer

Debnath,

Flood,

Raghavachari

2024

J. Phys. Chem. B

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Aromatic foldamers make up a novel class of bioinspired molecules that display helical conformations and have functions that rely on control over their coil−helix folding preferences. While the folding has been extensively examined by experiment, it has rarely been paired with the types of atomic level insights offered by theory. We present the results of all-atom molecular dynamics (MD) simulations to examine the role of solvent polarity on driving the helical folding behavior of the aryltriazole foldamer. The temperature-dependent enhanced sampling technique, replica-exchange MD simulations, was employed to understand the folding phenomena. The simulation results show that in a low polarity solvent (dichloromethane), the foldamer prefers to stay in the unfolded state. The unfolded state has four dipolar triazoles (5 D) in their favored all-anti geometries and favoring anti-parallel geometries. However, an increase in solvent polarity using acetonitrile resulted in solvophobic collapse, yielding the helically folded form as the predominant state. The folded helix has an all-syn geometry, with triazoles in parallel arrangements. Intermediate conformations with a mixture of syn and anti arrangements of the triazoles are of lower abundance in both the DCM and MeCN solvents. The chiral handedness of the helix observed experimentally is assigned as left-handed by correlation with computed electronic circular dichroism spectra using time-dependent density functional theory.

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“…The gelator contains the Oxd moiety that is an unnatural amino acid, readily obtained from threonine. The heterocyclic ring imparts a local constraint to the molecule, so that it can readily adopt stable secondary structures even with a reduced number of amino acid in the chain 54–56 . Some dipeptides and tripeptides containing the Oxd moiety act as gelator, both for water and for organic solvents 13,57 .…”

Section: Introductionmentioning

confidence: 99%

“…The heterocyclic ring imparts a local constraint to the molecule, so that it can readily adopt stable secondary structures even with a reduced number of amino acid in the chain. [54][55][56] Some dipeptides and tripeptides containing the Oxd moiety act as gelator, both for water and for organic solvents. 13,57 The dissolution of the gelator in a milder environment given by a phosphate buffer at pH 7.4 avoids the hydrolysis, allowing us to obtain materials stiffer than the ones obtained with dissolution in NaOH.…”

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confidence: 99%

A short oxazolidine‐2‐one containing peptide forms supramolecular hydrogels under controlled conditions

Ravarino

Giuri

Tomasini

2023

Journal of Peptide Science

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Low‐molecular‐weight hydrogels are made of a small percentage of small organic molecules dispersed in an aqueous medium, which may aggregate in several manners using different methods. However, often the organic gelator in water has poor solubility, so the addition of a solubilising agent is required. In the case of acidic gelators, this mainly consists of the addition of a strong base, that is sodium hydroxide, that deprotonates the acidic moiety, so the gelator molecules become more soluble and tend to assemble into micelles, forming a dispersion. Some gelators, however, are sensitive to the harsh pH and get hydrolysed. This is the case of some molecules presenting carbamates in their features, like Fmoc‐protected or oxazolidinone‐containing peptides. In this paper, we present a valid alternative to sodium hydroxide, by dissolving a tripeptide containing an oxazolidinone moiety in a phosphate buffer (PB) medium at pH 7.4. The results obtained with the NaOH dissolution are compared with the ones with PB, as both methods present advantages and drawbacks. The use of NaOH produces transparent but weak hydrogels, as it exposes the gelator to harsh conditions that end up in its partial hydrolysis, which is more pronounced at high concentrations (≥10 mM). Using PB to dissolve the gelator, this problem is completely avoided as no hydrolysis product has been detected in the hydrogels, which are very stiff although more opaque. By tuning the preparation conditions, we can obtain a wide variety of hydrogels, with the properties required by the final application.

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Elusive π-helical peptide foldamers spotted by chiroptical studies

Abstract: A series of oligomers containing alternate l-Ala and pGlu (pyroglutamic acid) both in the L and D form have been prepared and conformationally investigated by X-ray, NMR, UV/ECD, IR/VCD and molecular modelling.

Cited by 6 publications

References 67 publications

Dissecting the Supramolecular Dispersion of Fullerenes by Proteins/Peptides: Amino Acid Ranking and Driving Forces for Binding to C60

Dissecting the Supramolecular Dispersion of Fullerenes by Proteins/Peptides: Amino Acid Ranking and Driving Forces for Binding to C60

Solvent-Dependent Folding Behavior of a Helix-Forming Aryl-Triazole Foldamer

A short oxazolidine‐2‐one containing peptide forms supramolecular hydrogels under controlled conditions

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