Reconnaissance suprabiomoléculaire, foldamères et transport membranaire
Minisymposium chimie ED459
4 conférences par : Prof. Tomoki
Le Jeudi 22 Juin 2023 de 14h à 17h30
IEM, Salle de conférences (300 av. Émile-Jeanbrau, bât. 40)
Date de début : 2023-06-22 14:00:00
Date de fin : 2023-06-22 17:30:00
Lieu : IEM salle de conférences
Intervenant : Prof. Tomoki
Kyoto University, JP | IECB, Université de Bordeaux, FR | Université Libre de Bruxelles, BE | Université de Mons, BE
Programme
(mis à jour 2023-06-20 ; horaires indicatifs, ordre des conférences susceptible de remaniement)
14:00 – Prof. [marron]Tomoki
[bleu]Supramolecular assemblies and systems based on pillar-shaped macrocyclic compounds: “pillar[n]arenes”[/bleu]
14:45 – Dr. [marron]Gilles
[bleu]Taking inspiration from biopolymers – foldamers as protein mimics[/bleu]
15:30 – Dr. [marron]Hennie
[bleu]Overcoming challenges in anion transport: a story on phosphate, bicarbonate, and fluoride transport[/bleu]
16:15 – Dr. [marron]Mathieu
[bleu]Supramolecular assemblies inspired by biomolecules – from 1D to 2D chiral templates[/bleu]
17:30 – End
Contact local IBMM : Dr. Sébastien
Contact local IEM : Dr. Mihai
Résumés des conférences
Voir les illustrations dans les versions PDF jointes
1. Supramolecular assemblies and systems based on pillar-shaped macrocyclic compounds: “pillar[n]arenes”
Prof. [marron]Tomoki
Kyoto University, Japan
Macrocyclic compounds are key players in supramolecular chemistry because of their beautiful shape, nano-scale size and molecular recognition ability. In 2008, we reported a new class of macrocyclic hosts named “pillar[n]arenes”. They have unique symmetrical pillar structures due to their para-bridge linkage. We synthesized various supramolecular assemblies based on the polygonal tubular structures of pillar[n]arenes. In this lecture, chirality control, memory and amplification systems based on the dynamic planar chirality of pillar[n]arenes are also discussed.
2. Taking inspiration from biopolymers – foldamers as protein mimics
Dr. [marron]Gilles
CBMN, IECB Institut Européen de Chimie et Biologie, UMR 5248, CNRS, Université de Bordeaux, FR
The discovery that synthetic sequence-specific oligomers can adopt well-defined folded structures – foldamers [1] – has profoundly changed our view of biopolymer mimicry, raising prospects for exploring new chemical spaces and creating novel synthetic architectures with defined functions.[2–4] In this presentation, we will discuss some of our efforts towards this goal, showing how de novo design, careful structural investigation and subsequent sequence engineering of non-peptide helical foldamers may be used to generate effective peptide and protein mimics.
Besides aliphatic and aromatic oligoamide foldamers (β-peptides, peptoids, sulfono-γ-AApeptides, quinoline-based oligoamides, …) which have received much of the attention in the field, a few other backbones that do not contain an amide linkage but similarly show a high folding propensity (e.g. aliphatic urea-based oligomers studied in our group) have emerged. Oligourea foldamers which form well-defined and stable helical secondary structures (Fig. 1) reminiscent of the α-helix combine a number of characteristics ‒ synthetic accessibility, sequence modularity, folding fidelity, and stability to proteolysis ‒ that bode well for their use in various applications.[5]
Applications developed in our group with a focus on molecular recognition include the design of (i) bioactive peptide mimics with a reduced peptide character and improved pharmacological properties (i.e. modulators of protein-protein interactions and receptor ligands), (ii) foldamer-based organocatalysts as well as more sophisticated architectures like (iii) composite proteins and (iv) foldamer-based nanostructures.
Figure 1. [see illustration in attached PDF abstract]
Helical-wheel representations of α-peptide and oligourea backbones and X-ray structure of a helically-folded oligourea foldamer.
References
1. S. H. Gellman, Acc. Chem. Res. 1998, 31, 173–180.
2. G. Guichard, I. Huc, Chem. Commun. 2011, 47, 5933–5941.
3. W. S. Horne, T. N. Grossmann, Nat. Chem. 2020, 12, 331–337.
4. M. Pasco, C. Dolain, G. Guichard, In: S. Kubik (Ed.), Supramolecular chemistry in water, Wiley‐VCH Verlag GmbH & Co. KGaA Weinheim, Germany, 2019, pp. 337–374.
5. S. H. Yoo, B. Li, C. Dolain, M. Pasco, G. Guichard, In: E. J. Petersson (Ed.), Methods Enzymol. Vol. 656, Academic Press, 2021, pp. 59–92.
3. Overcoming challenges in anion transport: a story on phosphate, bicarbonate, and fluoride transport
Dr. [marron]Hennie
Engineering of Molecular NanoSystems, Université libre de Bruxelles, Belgium
Synthetic anion receptors are increasingly explored for the transport of anions across lipid membranes.[1] This research is warranted by the potential biological applications of anion transporters, which range from the replacement of defective proteins in diseases linked to anion transport (such as cystic fibrosis) to the disruption of homeostasis, leading to toxicity (anticancer and antimicrobial applications).[2]
The vast majority of the research on anion transport focusses on the transmembrane transport of chloride. While chloride is the most abundant anion in organisms, bicarbonate and phosphates play crucial roles in biology as well.[3] However, it is more difficult to design receptors for these non-spherical anions. Furthermore, H2PO4–, F–, and HCO3– are more strongly hydrated than Cl– and different (de)protonation equilibria have to be considered in the transmembrane transport process.
While many simple structures with urea/thiourea/squaramide groups show activity as chloride transporters, the efficient transport of bicarbonate and phosphate requires more sophisticated anion receptors, with 8–12 H-bond donors in macrocyclic structures. Here, I will present our recent breakthroughs in the transport of these more challenging anions,[4,5] including the first example of a phosphate transporter.
Figure 1. [see illustration in attached PDF abstract]
Compared to Cl–, the anions HCO3–, F–, and H2PO4– are increasingly difficult to transport across lipid membranes, requiring more advanced anion receptor designs.
References
1. J. T. Davis, P. A. Gale, R. Quesada, Advances in anion transport and supramolecular medicinal chemistry. Chem. Soc. Rev. 2020, 49(16), 6056–6086.
2. A. Roy, P. Talukdar, Recent Advances in Bioactive Artificial Ionophores. ChemBioChem 2021, 22(20), 2925–2940.
3. L. Martínez-Crespo, H. Valkenier, Transmembrane transport of bicarbonate by anion receptors. ChemPlusChem 2022, 87(11), e202200266.
4. L. Martínez‐Crespo, S. H. Hewitt, N. A. D. Simone, V. Šindelář, A. P. Davis, S. Butler, H. Valkenier, Transmembrane transport of bicarbonate unravelled. Chem. Eur. J. 2021, 27(26), 7367–7375.
5. A. Cataldo, M. Chvojka, G. Park, V. Šindelár, F. P. Gabbaï, S. J. Butler, H. Valkenier, Transmembrane transport of fluoride studied by time-resolved emission spectroscopy. [preprint] ChemRxiv 2023. https://doi.org/10.26434/chemrxiv-2023-b1780
4. Supramolecular assemblies inspired by biomolecules – from 1D to 2D chiral templates
Dr. [marron]Mathieu
Laboratory for Chemistry of Novel Materials, University of Mons, Belgium
Chirality is ubiquitous in Nature, down to the molecular scale as exemplified by the DNA double helix or the collagen triple helix. Inspired by these biomolecular constructs, our research is centered on the use of information-rich chiral templates to guide the organization of functional molecules for potential applications in delivery, imaging, and sensing.
In this seminar, we first discuss examples of DNA-templated 1D assemblies, for which we observed the effects of sequence and length on the supramolecular assembly of π-conjugated (macro)molecules.[1] This is harnessed to photo-modulate the organization of multi-chromophoric systems, or to probe an enzymatic activity in real time.[2-3] We then report the development of peptide surfaces as 2D chiral templates. Through the development of layers mimicking a collagen matrix, we show that epithelial cells migrate differently on mirror-image surfaces. We discuss on how chirality can effectively influence cell migration through interactions between the cytoskeleton and the self-assembled peptides.[4]
References
1. M. Surin, S. Ulrich, Chem. Open 2020, 9, 480.
2. J. Rubio-Magnieto, T.-A. Phan, M. Fossépré, V. Matot, J. Knoops, T. Jarrosson, P. Dumy, F. Serein-Spirau, C. Niebel, S. Ulrich, M. Surin, Chem. Eur. J. 2018, 24, 706.
3. M. Fossépré, M. Trévisan, V. Cyriaque, R. Wattiez, D. Beljonne, S. Richeter, S. Clément, M. Surin, ACS Appl. Bio Mater. 2019, 2, 2125.
4. G. Lebreton, C. Géminard, F. Lapraz, S. Pyrpassopoulos, D. Cerezo, P. Spéder, E. M. Ostap, S. Noselli, Science 2018, 362, 949.
