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Ivan Huc

Publications and source records attributed to Ivan Huc.

At least 19 recordsLinked to original sources
PubMed2006

Amphipathic helices from aromatic amino acid oligomers.

Synthetic helical foldamers are of significant interest for mimicking the conformations of naturally occurring molecules while at the same time introducing new structures and properties. In particular, oligoamides of aromatic amino acids are attractive targets, as their folding is highly predictable and stable. Here the design and synthesis of new amphipathic helical oligoamides based on quinoline-derived amino acids having either hydrophobic or cationic side chains are described. Their structures were characterized in the solid state by single-crystal X-ray diffraction and in solution by NMR. Results of these studies suggest that an oligomer as short as a pentamer folds into a stable helical conformation in protic solvents, including MeOH and H(2)O. The introduction of polar proteinogenic side chains to these foldamers, as described here for the first time, promises to provide possibilities for the biological applications of these molecules. In particular, amphipathic helices are versatile targets to explore due to their importance in a variety of biological processes, and the unique structure and properties of the quinoline-derived oligoamides may allow new structure-activity relationships to be developed.

Amino Acids, Aromatic↗
PubMed2006

Asp-Gly based peptides confined at the surface of cationic gemini surfactant aggregates.

Cationic gemini surfactants complexed with anionic oligoglycine-aspartate (called gemini peptides hereafter) were synthesized, and their aggregation behaviors were studied. The effects of the hydrophobic chain length (C10-C22) and the length of the oligoglycine (0-4) were investigated, and it was clearly shown by critical micellar concentration, Krafft temperature, and isothermal surface pressure measurements that the hydrophobic effect and interpeptidic interaction influence the aggregation behavior in a cooperative manner. Below their Krafft temperatures, some of them formed both hydro- and organogels with three-dimensional networks and the Fourier transform infrared measurements show the presence of interpeptidic hydrogen bonds.

Aspartic Acid↗
PubMed2005

Probing helix propensity of monomers within a helical oligomer.

A simple strategy is proposed to assess the propensity of a given monomer to follow or not follow a particular helical scheme and to study helix reversal phenomena within helical oligomers. It consists of placing a monomer having a low helix propensity between two conformationally stable helical segments. Helix reversion then occurs preferentially at the site of this monomer, leading to the formation of isomers having P (right-handed) or M (left-handed) helicities at each of the two helical segments. The proportion between the P-P/M-M and P-M isomers is indicative of the stereochemical relations between the inserted monomer and the helical frame. Thus, xylylene or carboxylic acid anhydride spacers have been introduced between two helical oligoamides of 8-amino-2-quinolinecarboxylic acid. Both these spacers presumably lack some of the structural features that confer quinoline units with a high helix propensity. Only one species is observed in solution in the case of an anhydride spacer. This species was shown by x-ray crystallography to be a racemic mixture of P-P and M-M helices. Unexpectedly, the anhydride is consistently incorporated within helical oligoamides. For the xylylene spacer, the P-P/M-M racemate and P-M meso compound are in equal proportions in chloroform, showing that this spacer does not have a propensity to adopt any helical conformation in this solvent. However, the equilibria between the various isomers are shifted in toluene, where one species largely prevails. This species was shown by x-ray crystallography to be the P-P/M-M racemate. Molecular dynamics simulations are consistent with these solution data.

Journal Article↗
PubMed2005

Solution structure of quinoline- and pyridine-derived oligoamide foldamers.

The unambiguous elucidation of a new folded structure in solution may prove to be a very challenging task. The NMR protocols developed for solving the solution structures of alpha-peptides have been applied to aliphatic beta- and gamma-peptides but are not directly applicable to aromatic oligomers. In particular, the string of spin systems in an aromatic sequence cannot be reconstituted solely from correlations between protons. For aromatic oligomers, it is shown that the assignment of a large part of the 13C NMR spectrum through HMBC and HSQC experiments allows to unambiguously assign proton NMR spectra and in turn to interpret NOE correlations. This has been implemented both with quinoline- and pyridine-derived oligoamide foldamers, and should be applicable to a wide range of oligomers including various combinations of monomers. The NOE correlations allow the unambiguous solution structure elucidation of helical conformations of oligoamides derived from pyridine and quinoline monomers showing that, in these series, the solution structures correspond very well to the structures observed in the solid state.

Amides↗
PubMed2005

Chiral induction in quinoline-derived oligoamide foldamers: assignment of helical handedness and role of steric effects.

Chiral groups attached to the end of quinoline-derived oligoamide foldamers give rise to chiral helical induction in solution. Using various chiral groups, diastereomeric excesses ranging from 9% to 83% could be measured by NMR and circular dichroism. Despite these relatively weak values and the fact that diastereomeric helices coexist and interconvert in solution, the right-handed or left-handed helical sense favored by the terminal chiral group could be determined unambiguously using X-ray crystallography. Assignment of chiral induction was performed in an original way using the strong tendency of racemates to cocrystallize, and taking advantage of slow helix inversion rates, which allowed one to establish that the stereomers observed in the crystals do correspond to the major stereomers in solution. The sense of chiral helical induction was rationalized on the basis of sterics. Upon assigning an Rs or Ss chirality to the stereogenic center using a nomenclature where the four substituents are ranked according to decreasing sizes, it is observed that Rs chirality always favors left-handed helicity and Ss chirality favors right-handed helicity (P). X-ray structures shed some light on the role of sterics in the mechanism of chiral induction. The preferred conformation at the stereocenter is apparently one where the bulkiest group should preferentially point away from the helix, the second largest group should be aligned with the helix backbone, and the smallest should point to the helix.

Amides↗
PubMed2004

Strained aromatic oligoamide macrocycles as new molecular clips.

Can one join both ends of a helix? A helical aromatic oligoamide was macrocyclized into a saddle-shaped bifunctional clip molecule that self-assembles into discrete circular dodecamers in the solid state and shows great potential for binding aromatic acid guests in solution. The cyclization step requires that the helix is only partly denatured in the reaction medium.

Journal Article↗
PubMed2004

Design of an inversion center between two helical segments.

A new strategy is proposed to control the relative orientation of two folded helical oligomers in such a way that they diverge from an aromatic linker and have opposite helical handedness. Mutual steric exclusion between the two helices results from the fact that they cannot be at the same time folded and on the same side of the linker. The concept is validated using the helical conformations of oligoamides of 8-amino-2-quinolinecarboxylic acid, but it should be applicable to many families of oligomers and leads to the first designed meso-helices.

Biomimetic Materials↗
PubMed2004

Switching of chiral induction in helical aromatic oligoamides using solid state-solution state equilibrium.

The introduction of an R asymmetric center in an aromatic oligoamide that adopts stable helical conformations leads to a significant shift of the equilibrium between the right-handed and left-handed helices in solution: the R-P and R-M helices are diastereoisomers. However, these two species were found to cocrystallize in 1:1 proportions. Thus the chiral induction observed in solution is switched off in the solid state. This phenomenon represents an original and unexpected means to control handedness in helical oligomers.

Journal Article↗
PubMed2003

Aromatic delta-peptides.

Oligoamides of 8-amino-2-carboxy-quinoline adopt a very stable helical conformation characterized in solution by 1H NMR and in the solid state by single-crystal X-ray diffraction. The helix comprises only 2.5 units per turn, which represents the highest curvature achieved by aromatic oligoamides until now. Monomers possessing alkoxy substituents in position 4 are easily available from 2-nitroaniline and dimethyl acetylenedicarboxylate.

Models, Molecular↗