A Non‐coded β<sup>2,2</sup>‐Amino Acid with Isoxazoline Core Able to Stabilize Peptides Folding through an Unprecedented Hydrogen Bond

Bucci, Raffaella; Vaghi, Francesco; Lorenzo, Davide Di; Anastasi, Francesco; Broggini, Gianluigi; Presti, Leonardo Lo; Contini, Alessandro; Gelmi, Maria Luisa

doi:10.1002/ejoc.202200601

Cited by 5 publications

(3 citation statements)

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“…In order to continue our researches in finding noncoded amino acids by using cycloaddition reactions, − we here present a suitable alternative that avoids complex combinations (polymer and coating) and cumbersome syntheses, that is, the use of a pristine peptide for electrospinning of biocompatible nanofibers. The non-coded amino acids are synthesized by a single step, scalable, and straightforward cycloaddition reaction by commercially available starting materials, that are diazoalkanes and maleimids, − which create pyrrolo-pyrazole building blocks 3 simulating γ-amino acids (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Smart Electrospun Nanofibers from Short Peptidomimetics Based on Pyrrolo-pyrazole Scaffold

Chiesa,

Clerici,

Bucci

et al. 2024

Biomacromolecules

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We prepared a small library of short peptidomimetics based on 3-pyrrolo-pyrazole carboxylate, a non-coded γ-amino acid, and glycine or alanine. The robust and eco-friendly synthetic approach adopted allows to obtain the dipeptides in two steps from commercial starting materials. This gives the possibility to shape these materials by electrospinning into microand nanofibers, in amounts required to be useful for coating surfaces of biomedical relevance. To promote high quality of electrospun fibers, different substitution patterns were evaluated, all for pure peptide fibers, free of any polymer or additive. The best candidate, which affords a homogeneous fibrous matrix, was prepared in larger amounts, and its biocompatibility was verified. This successful work is the first step to develop a new biomaterial able to produce pristine peptidebased nanofibers to be used as helpful component or stand-alone scaffolds for tissue engineering or for the surface modification of medical devices.

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Section: Introductionmentioning

confidence: 99%

Smart Electrospun Nanofibers from Short Peptidomimetics Based on Pyrrolo-pyrazole Scaffold

Chiesa,

Clerici,

Bucci

et al. 2024

Biomacromolecules

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“…Hence, indirect detection of VI was planned. We chose a nitrile oxide as a trapping agent, as this 1,3-dipole is known to regioselectively react with electron-poor dipolarophiles . After a 15 min exposure of 2-(bromomethyl)acrylate to triphenylphosphine and triethylamine, the addition of chloroxime 7 and triethylamine (to generate benzonitrile oxide) afforded the centrosymmetric bis-isoxazoline 8 as the sole product (Scheme ).…”

mentioning

confidence: 99%

“…We chose a nitrile oxide as a trapping agent, as this 1,3-dipole is known to regioselectively react with electron-poor dipolarophiles. 11 After a 15 min exposure of 2-(bromomethyl)acrylate to triphenylphosphine and triethylamine, the addition of chloroxime 7 and triethylamine (to generate benzonitrile oxide) afforded the centrosymmetric bis-isoxazoline 8 as the sole product ( Scheme 5 ). Again, the double cycloaddition was totally regio- and stereoselective, as confirmed by X-ray diffraction analysis of a single crystal of 8 .…”

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confidence: 99%

Phosphine-Catalyzed Domino Regio- and Stereo-Selective Hexamerization of 2-(Bromomethyl)acrylates to 1,2-Bis(cyclohexenyl)ethenyl Derivatives

Papis,

Bucci,

Contini

et al. 2023

Org. Lett.

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A phosphine-catalyzed domino assembly of six units of 2-bromomethyl acrylates afforded polyalkenyl adducts containing two cyclohexenyl rings. This reaction occurs under mild conditions providing the final product by formation of seven carbon−carbon bonds and four stereocenters. Experimental and computational studies support an initial dimerization of the substrate, which in turn trimerizes involving two totally regio-and stereocontrolled Diels−Alder cycloadditions. The yield of the hexamerization of the 2bromomethyl acrylates depends on the size of the ester function. The protocol has also proved to be practicable on a gram scale.

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An experimental and computational investigation of the cyclopentene-containing peptide-derived compounds: focus on pseudo-cyclic motifs via intramolecular interactions

Bojarska,

Breza,

Borowiecki

et al. 2024

R. Soc. Open Sci.

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Conformational flexibility is one of the main disadvantages of peptide-based compounds. We focus on their molecular ‘chameleonicity’ related to forming pseudo-cyclic motifs via modulation of weak intramolecular interactions. It is an appealing strategy for controlling equilibrium between the polar open and the nonpolar closed conformations. Within this context, we report here the crystal structure of the ( R )-(2- tert -butoxycarbonyl)amino-1-oxo-3-phenyl)propyl)-1-cyclopentene ( 1 ), synthesis of which in high yield was achieved by a facile multi-step protocol. Our Cambridge Structural Database (CSD) overview for the peptide-based crystals revealed the exclusivity of this compound from the viewpoint of the unusual pseudo-bicyclic system via C–H … O and C–O … π interactions, in which cyclopentene shields the amide bond. Notably, cyclopentene as a bioisostere of proline is an appealing scaffold in medicinal chemistry. An extensive combined experimental and computational study provided more profound insight into the supramolecular landscape of 1 with respect to similar derivatives deposited in the CSD, including the tendency of cyclopentene for the generation of pseudo-cyclic motifs through weak H-bonding and π-based intramolecular interactions. These weak interactions have been examined by either the quantum theory of ‘atoms-in-molecules’ (QTAIM) or complex Hirshfeld surface methodology, including enrichment ratios, molecular electrostatic potential surfaces and energy frameworks. In all analysed crystals, all types of H-bonded motifs involving cyclopentene are formed at all levels of supramolecular architecture. A library of cyclopentene-based H-bonding synthons is provided. A molecular docking study depicted vital interactions of cyclopentene with key amino acid residues inside the active sites of two prominent protein kinases, uncovering the therapeutic potential of 1 against breast cancer. To a large extent, dispersion forces have significance in stabilizing the supramolecular structure of both ligand and bio-complex ligand–protein. Finally, the satisfactory in silico bio-pharmacokinetic profile of 1 related to drug-likeness and blood–brain barrier permeation was also revealed.

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A Non‐coded β^2,2‐Amino Acid with Isoxazoline Core Able to Stabilize Peptides Folding through an Unprecedented Hydrogen Bond

Abstract: Dedicated to Prof. Cesare Gennari on the occasion of his 70th birthday.

Cited by 5 publications

References 65 publications

Smart Electrospun Nanofibers from Short Peptidomimetics Based on Pyrrolo-pyrazole Scaffold

Smart Electrospun Nanofibers from Short Peptidomimetics Based on Pyrrolo-pyrazole Scaffold

Phosphine-Catalyzed Domino Regio- and Stereo-Selective Hexamerization of 2-(Bromomethyl)acrylates to 1,2-Bis(cyclohexenyl)ethenyl Derivatives

An experimental and computational investigation of the cyclopentene-containing peptide-derived compounds: focus on pseudo-cyclic motifs via intramolecular interactions

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A Non‐coded β2,2‐Amino Acid with Isoxazoline Core Able to Stabilize Peptides Folding through an Unprecedented Hydrogen Bond

Abstract: Dedicated to Prof. Cesare Gennari on the occasion of his 70th birthday.

Cited by 5 publications

References 65 publications

Smart Electrospun Nanofibers from Short Peptidomimetics Based on Pyrrolo-pyrazole Scaffold

Smart Electrospun Nanofibers from Short Peptidomimetics Based on Pyrrolo-pyrazole Scaffold

Phosphine-Catalyzed Domino Regio- and Stereo-Selective Hexamerization of 2-(Bromomethyl)acrylates to 1,2-Bis(cyclohexenyl)ethenyl Derivatives

An experimental and computational investigation of the cyclopentene-containing peptide-derived compounds: focus on pseudo-cyclic motifs via intramolecular interactions

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A Non‐coded β^2,2‐Amino Acid with Isoxazoline Core Able to Stabilize Peptides Folding through an Unprecedented Hydrogen Bond