Self-Assembled Protein–Aromatic Foldamer Complexes with 2:3 and 2:2:1 Stoichiometries

Jewgiński, Michał; Granier, T.; d’Estaintot, Béatrice Langlois; Fischer, Lucile; Mackereth, Cameron D.; Huc, Ivan

doi:10.1021/jacs.7b00184

Cited by 25 publications

(21 citation statements)

References 40 publications

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“…INEDA and NEDA protocols can be used to identify and quantify a variety of intramolecular and intermolecular interactions in foldamer segments composed of different non‐natural monomers, especially as a part of foldamer computational studies . INEDA can be applied to other systems as well, such as foldamer‐biopolymer complexes, foldamer‐enclosed guest molecules, synthetic polymers, biopolymers (particularly enzymes), and molecules adsorbed on surfaces. The information extracted from INEDA and NEDA can then be used to interpret geometric, energetic, or spectroscopic, properties in such systems.…”

Section: Discussionmentioning

confidence: 99%

Intramolecular Natural Energy Decomposition Analysis: Applications to the Rational Design of Foldamers

Sproviero

2018

J Comput Chem

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We describe an intramolecular version of the natural energy decomposition analysis (NEDA), with the aim of evaluating interactions between molecular fragments across covalent bonds. The electronic energy in intramolecular natural energy decomposition analysis (INEDA) is divided into electrical, core, and charge transfer components. The INEDA method describes the fragments using the nonfragmented electronic density, and, therefore, there are no limitations in how to choose the boundary orbital. We used INEDA to evaluate the interaction energies that give origin to barriers of rotation around C C (C C ) and N C (N C ) bonds in arylamide-foldamer building blocks. We found that differences of barrier height between models with different ortho-aryl substituents stem from charge transfer and core interactions. In three-center hydrogen-bond (H-bond) models with an NH proton donor H-bound to two electronegative ortho-aryl substituents, the interaction energy of the three-center system is larger than in either of the two-center H-bond subsystem alone, indicating an increase of overall rigidity. The combination of INEDA and NEDA allows the evaluation of intermolecular and intramolecular interactions using a consistent theoretical framework. © 2018 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Intramolecular Natural Energy Decomposition Analysis: Applications to the Rational Design of Foldamers

Sproviero

2018

J Comput Chem

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“… 94 Additionally, there is a strong foldamer sequence dependence of the assembly behavior. 95 Novel protein–foldamer stoichiometries were observed with, as an exceptional highlight, the structural elucidation of a protein–foldamer complex consisting of two proteins and three foldamers. Two of the foldamers are bound to the HCA via a ligand, and the third foldamer is sandwiched between these two foldamers as a kind of molecular glue.…”

Section: Protein Assembly and Modulationmentioning

confidence: 99%

Supramolecular Chemistry Targeting Proteins

et al. 2017

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The specific recognition of protein surface elements is a fundamental challenge in the life sciences. New developments in this field will form the basis of advanced therapeutic approaches and lead to applications such as sensors, affinity tags, immobilization techniques, and protein-based materials. Synthetic supramolecular molecules and materials are creating new opportunities for protein recognition that are orthogonal to classical small molecule and protein-based approaches. As outlined here, their unique molecular features enable the recognition of amino acids, peptides, and even whole protein surfaces, which can be applied to the modulation and assembly of proteins. We believe that structural insights into these processes are of great value for the further development of this field and have therefore focused this Perspective on contributions that provide such structural data.

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“…Interactions were first detected through induction of foldamer helix handedness in response to contacts with chiral elements at the protein surface, and subjected to structural investigations both in the solid state and in solution . Crystal structures proved their usefulness in that they revealed multiple features that could not have been designed in the first place, including unusual foldamer–protein complex stoichiometries, and now constitute starting points for iterative improvements. They also relate to crystal structures of complexes between proteins and other medium‐sized aromatic ligands such as calixarenes, suramine, 1,3,6,8‐pyrenetetrasulfonic acid, or molecular tweezers …”

Section: Figurementioning

confidence: 99%

Structure Elucidation of Helical Aromatic Foldamer–Protein Complexes with Large Contact Surface Areas

Reddy

d’Estaintot

Granier

et al. 2019

Chemistry A European J

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The development of large synthetic ligands could be useful to target the sizeable surface areas involved in protein-protein interactions.H erein,w ep resent long helical aromatic oligoamide foldamersb earing proteinogenic side chainst hat cover up to 450 2 of the human carbonic anhydrase II (HCA) surface. The foldamers are composed of aminoquinolinecarboxylic acids bearing proteinogenic side chains and of more flexible aminomethyl-pyridinecarboxylic acids that enhance helix handedness dynamics. Crystal structures of HCA-foldamer complexes were obtained with a9 -a nd a1 4-mer both showing extensive protein-foldamer hydrophobic contacts. In addition, foldamer-foldamer interactions seem to be prevalent in the crystal packing, leading to the peculiar formation of an HCA superhelix wounda round ar od of stacked foldamers. Solution studies confirmt he positioning of the foldamer at the protein surface as well as ad imerization of the complexes.Aromatic foldamers [1] emerge as an ew class of folded oligomers that may be decorated with proteinogenic side chains to interactw ith proteins [2,3] and nucleic acids, [4,5] ande ventually serve as inhibitors of nucleic acid-protein andp rotein-protein interactions. Amphipathic structures have also been shown to interactw ith, or to insert themselves in,m embranes. [6, 7] Some possess antibiotic activity. [6] Both linear [2,5, 6] and helical [3, 4, 7] foldamers have been developed and varied targets have been identified, including hDM2 and B-cell lymphoma-2 (Bcl-2)r egulator proteins, [2a,d,e] protein precursors of amyloids, [2c, 3a-e] G-quadruplex DNA [4] and some DNA-binding enzymes. [3f] Advantages of aromatic foldamersi nclude their ease of synthesis, for example through solid-phasem ethodologies, [8] and the predictability and stability of their folded conformations in both protica nd aprotics olvents. [9] Becauser elativelyl arge and welldefined folded objects can be produced using aromatic amide backbones, [10] it mayb ee nvisaged to cover large surfacea reas of proteins and nucleic acids. For example, we recently reported protein binding using a9 .2 kDa foldamer mimicking a 16 base-pair DNA duplex. [3f] Nevertheless, designing objects that can recognize large surfacea reas of proteins is difficult: whichs ide chains are to be selecteda nd where should they be located?S ome of the published work concerned mimetics of a-helices, [2] B-DNA, [3f] or natural products. [5] Other approachesuse screening through directed evolution methods. [11] It remains that no general approache xists for the ab initio designo fl arge ligands for ap roteins urface. Structurali nformationa bout aromatic foldamer-protein interactions would constitute af irm stepping-stonef or further design,b ut it can hardlyb eo btained without having reasonable binding affinity in the first place.To overcomet his sort of deadlock, we endeavoredt oi nvestigate foldamer-protein interfaces by confining foldamers at the surface of ap rotein. [12, 13] For example, helical oligoamides based on 8-aminoqu...

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Self-Assembled Protein–Aromatic Foldamer Complexes with 2:3 and 2:2:1 Stoichiometries

Cited by 25 publications

References 40 publications

Intramolecular Natural Energy Decomposition Analysis: Applications to the Rational Design of Foldamers

Intramolecular Natural Energy Decomposition Analysis: Applications to the Rational Design of Foldamers

Supramolecular Chemistry Targeting Proteins

Structure Elucidation of Helical Aromatic Foldamer–Protein Complexes with Large Contact Surface Areas

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