CONNECT | From Supramolecular to Covalent Boron Clusters Membrane Carriers

Summary
Conceptually new synthetic membrane transporters constitute a key challenge for supramolecular chemistry and materials sciences. To date, the transport of hydrophilic bioactive substances across membranes has exploited the amphiphilic character of carriers and cargos such as in lipids or other cationic amphiphiles. However, amphiphilic molecules face limitations due to intrinsic features such as toxicity associated to their detergent-like behaviour and their tendency to aggregate. This year, it has been described that superchaotropic boron clusters can transport a range of hydrophilic chemical substances across lipid membranes and inside cells. This new concept supports that the chaotropic effect can guide the design of an entirely new class of membrane carriers. However, until now, boron clusters have only been used as non-covalent carriers of the cargo of interest. The main objective of this action is to investigate, for the first time, the covalent introduction of superchaotropic substituents into prototype peptide sequences and evaluate their potential to be self-transported across membranes. A selection of simple anionic, cationic and hydrophobic peptides will be equipped with boron clusters modified amino acids and screened in model membranes and in cell assays. Unknown concepts and revolutionary molecules could emerge from this initial study. For example, the introduction of anionic boron clusters into cationic short peptides could give rise to a new class of (strongly hydrophilic) zwitterionic self-transported biomolecular scaffolds. We also suspect that switching hydrophobic for anionic chaotropic residues will decrease aggregation propensity but increase membrane transport efficiency of amphiphilic bioactive peptides. This new application of chaotropic cluster will impact the field of membrane transport by using more controllable, non-aggregating and less toxic synthetic vehicles.
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Web resources: https://cordis.europa.eu/project/id/101110303
Start date: 01-06-2023
End date: 31-05-2025
Total budget - Public funding: - 165 312,00 Euro
Cordis data

Original description

Conceptually new synthetic membrane transporters constitute a key challenge for supramolecular chemistry and materials sciences. To date, the transport of hydrophilic bioactive substances across membranes has exploited the amphiphilic character of carriers and cargos such as in lipids or other cationic amphiphiles. However, amphiphilic molecules face limitations due to intrinsic features such as toxicity associated to their detergent-like behaviour and their tendency to aggregate. This year, it has been described that superchaotropic boron clusters can transport a range of hydrophilic chemical substances across lipid membranes and inside cells. This new concept supports that the chaotropic effect can guide the design of an entirely new class of membrane carriers. However, until now, boron clusters have only been used as non-covalent carriers of the cargo of interest. The main objective of this action is to investigate, for the first time, the covalent introduction of superchaotropic substituents into prototype peptide sequences and evaluate their potential to be self-transported across membranes. A selection of simple anionic, cationic and hydrophobic peptides will be equipped with boron clusters modified amino acids and screened in model membranes and in cell assays. Unknown concepts and revolutionary molecules could emerge from this initial study. For example, the introduction of anionic boron clusters into cationic short peptides could give rise to a new class of (strongly hydrophilic) zwitterionic self-transported biomolecular scaffolds. We also suspect that switching hydrophobic for anionic chaotropic residues will decrease aggregation propensity but increase membrane transport efficiency of amphiphilic bioactive peptides. This new application of chaotropic cluster will impact the field of membrane transport by using more controllable, non-aggregating and less toxic synthetic vehicles.

Status

SIGNED

Call topic

HORIZON-MSCA-2022-PF-01-01

Update Date

31-07-2023
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.2 Marie Skłodowska-Curie Actions (MSCA)
HORIZON.1.2.0 Cross-cutting call topics
HORIZON-MSCA-2022-PF-01
HORIZON-MSCA-2022-PF-01-01 MSCA Postdoctoral Fellowships 2022