Prevalence of Eight-Membered Hydrogen-Bonded Rings in Some Bis(cyclobutane) β-Dipeptides Including Residues with Trans Stereochemistry

Torres, Elisabeth; Gorrea, Esther; Silva, Éric Da; Nolis, Pau; Branchadell, Vicenç; Ortuño, Rosa M.

doi:10.1021/ol900636w

Cited by 50 publications

(46 citation statements)

References 19 publications

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“…In ACBA polymers of mixed chirality, a structural transition between the aforementioned twofold was hypothesized for the cis-trans isomer, never reported previously. The local chirality controlled global fold preference prompted a systematic research on how local stereochemistry precludes the formation of mixed or inherently flexible secondary structures for β-peptides composed of [ACBA] n (Torres et al 2009;Gorrea et al 2012). However, the bases of a rigid scaffold design and the predictive power of such an approach strongly relies on the exact and explicit knowledge of the conformational preference of ACBA building units.…”

Section: Introductionmentioning

confidence: 99%

“…However, the bases of a rigid scaffold design and the predictive power of such an approach strongly relies on the exact and explicit knowledge of the conformational preference of ACBA building units. Even though the structural properties of ACBA oligomers were thoroughly analyzed by NMR and QM methods (Torres et al 2009), the precise abundance of all forms of these building units needs now to be proven experimentally. Although the QM and NMR results agreed well, the latter technique only measures on a conformational average, and thus it unravels properties of the individual foldamers.…”

Section: Introductionmentioning

confidence: 99%

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Foldamers of β-peptides: conformational preference of peptides formed by rigid building blocks. The first MI-IR spectra of a triamide nanosystem

et al. 2013

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IntroductionAlthough dynamic on a large timescale of motion, some biologically active polyamide nanosystems adopt welldefined 3D structures in a time average manner, called as globular proteins; a given name reflecting to their overall shape. Other proteins called intrinsically unstructured or dynamic (IUP or IDP) are reluctant to present such an easy to characterize structural ensemble, nicknamed as proteins with random structures. Thus, proteins exist in most phases as conformational ensembles presenting lower, while in other environment higher time average deviation from their average 3D folds. The α-amino acid sequence modification of these inherently dynamic polyamide systems can lower, or increase the amplitude and frequency of such internal motion, making the protein fold less or more -mobile‖. The chemical constitution (α) and the stereochemistry (L) of proteogenic amino acid residues are under strict evolutional conservation. Unlike L-Proline, all the remaining 19 common residues in proteins have two adjacent backbone torsional angles, φ and ψ, of high rotational freedom followed by the inflexible ω. The scenario of two flexible followed by a fixed backbone torsional angles per residue determines primarily the folding ability of a proteogenic polypeptide. Cutting of a globular fold seldom results in secondary structural elements (e.g. α-helix, β-turn) of low internal dynamics! Typically the removal of any secondary structural element from its -natural environment‖ results in polypetides of very elevated internal dynamics, often characterized as unstructured subunits. However, bioengineering requires stable toolkits to design epitopes, matching complementary folds, individual foldamers, nano-lego elements etc. of traceable shape and of low internal mobility. Shedding light on folding and stability of secondary structural elements of peptides and proteins could help to design standalone foldamers. They could be composed of β-, α-and α/β-amino acid residues, the latter called chimera. A general expectation of foldamers is to present a single time average 3D-structure of lower internal dynamics over the large timescale of picoseconds to second. These fold optimized biocompatible and nonnatural peptides often have an increased proteolytic and metabolic stability and can fulfill diverse biological functions toward DNA, RNA, ATP, etc. The improved ability of β-peptides and thus β-foldamers to rapidly and spontaneously fold (

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Foldamers of β-peptides: conformational preference of peptides formed by rigid building blocks. The first MI-IR spectra of a triamide nanosystem

et al. 2013

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“…This behaviour is different from that observed for the cis,cis- [9] and the cis,-trans-isomeric b-dipeptides, which have a lower tendency to form gels or regular fibres. Bearing in mind the possible applications of compounds 1 and 2 and related products, we wanted to gain knowledge concerning the formation and features of these aggregates as proof of the ability of the cyclobutane ring to induce the formation of defined structures not only in solution, [9,10,12,13] but as the result of molecular self-assembly. [9b,d] High-resolution NMR spectroscopy studies allowed us to investigate the dynamics of the gel formation process and the sol-gel transition temperature in toluene for both dipeptides 1 and 2.…”

Section: Introductionmentioning

confidence: 99%

Self‐Assembly of Chiral trans‐Cyclobutane‐Containing β‐Dipeptides into Ordered Aggregates

Gorrea

Nolis

Torres

et al. 2011

Chemistry A European J

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Two chiral synthetic β-dipeptides have been constructed, one with two trans-cyclobutane residues and the other with one trans and one cis fragment, 1 and 2, respectively, and investigated to get insight into the non-covalent interactions responsible for their self-assembly to form ordered aggregates, as well into parameters such as their morphology and size. Experimental evidence of the formation of these assemblies was provided by spectroscopy, microscopy and X-ray diffraction experiments that suggest the formation of nanoscale helical aggregates. This process involves a conformational change in the molecules of each dipeptide with respect to the preferred conformation of the isolated molecules in solution. A high-resolution NMR spectroscopy study allowed the determination of the dynamics of the gelation process in [D(8)]toluene and the sol-gel transition temperature, which was around 270 K in this solvent at a concentration of 15 mM. NMR spectroscopy experiments also provided some information about conformational changes involved in the sol-gel transition and also suggested a different gel packing for each dipeptide. These observations have been nicely explained by computational studies. The self-assembly of the molecules has been modelled and suggested a head-to-head molecular arrangement for 1 and a head-to-tail arrangement for 2 to give helical structures corresponding to hydrogen-bonded single chains. These chains interact with one another in an antiparallel way to afford bundles, the significant geometry parameters of which fit well to the main peaks observed in wide-angle X-ray diffraction spectra of the aggregates in the solid state.

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“…13,14,15 Moreover, a β-peptide composed of four cis-β-ACBC 1a residues has shown molecular self-assembly to form nanosized fibrils and gels, 16 and trans,trans-and trans,cis-bis(cyclobutane)-β-dipeptides show a tendency to assemble into nanoscale fibres. 17,18 Another reason for the enhanced interest in carbocyclic β-amino acids is the biological activity of some of these constrained compounds, e.g. cis-2-aminocyclopentanecarboxylic acid 2 (cispentacin) which has shown antifungal activity against various Candida strains.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel β-aminocyclobutanecarboxylic acid derivatives by a solvent-free aza–Michael addition and subsequent ring closure

2011

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Novel b-aminocyclobutanecarboxylic acid derivatives were prepared via a sequential solvent-free aza-Michael addition of benzophenone imine across 3-halopropylidenemalonates and base-induced ring closure. These highly substituted cyclobutanedicarboxylic acid derivatives were subjected to a reactivity study which demonstrated the tendency of these donor-acceptor substituted four-membered rings to be converted into their corresponding ring-opened products.

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Prevalence of Eight-Membered Hydrogen-Bonded Rings in Some Bis(cyclobutane) β-Dipeptides Including Residues with Trans Stereochemistry

Cited by 50 publications

References 19 publications

Foldamers of β-peptides: conformational preference of peptides formed by rigid building blocks. The first MI-IR spectra of a triamide nanosystem

Foldamers of β-peptides: conformational preference of peptides formed by rigid building blocks. The first MI-IR spectra of a triamide nanosystem

Self‐Assembly of Chiral trans‐Cyclobutane‐Containing β‐Dipeptides into Ordered Aggregates

Synthesis of novel β-aminocyclobutanecarboxylic acid derivatives by a solvent-free aza–Michael addition and subsequent ring closure

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