Photoswitchable Calixarene Activators for Controlled Peptide Transport across Lipid Membranes.

Supramolecular synthetic transporters are crucial to understand and activate the passage across lipid membranes of hydrophilic effector molecules. Herein, we introduce photoswitchable calixarenes for the light-controlled transport activation of cationic peptide cargos across model lipid bilayers and inside living cells. Our approach was based on rationally designed p-sulfonatocalix[4]arene receptors equipped with a hydrophobic azobenzene arm, which recognize cationic peptide sequences at the nM range. Activation of membrane peptide transport is confirmed, in synthetic vesicles and living cells, for calixarene activators featuring the azobenzene arm in the E configuration. Therefore, this method allows the modulation of the transmembrane transport of peptide cargos upon Z-E photoisomerization of functionalized calixarenes using 500 nm visible light. These results showcase the potential of photoswitchable counterion activators for the light-triggered delivery of hydrophilic biomolecules and pave the way for potential applications in remotely controlled membrane transport and photopharmacology applications of hydrophilic functional biomolecules.

Selective Recognition of Amino Acids and Peptides by Small Supramolecular Receptors.

To this day, the recognition and high affinity binding of biomolecules in water by synthetic receptors remains challenging, while the necessity for systems for their sensing, transport and modulation persists. This problematic is prevalent for the recognition of peptides, which not only have key roles in many biochemical pathways, as well as having pharmacological and biotechnological applications, but also frequently serve as models for the study of proteins. Taking inspiration in nature and on the interactions that occur between several receptors and peptide sequences, many researchers have developed and applied a variety of different synthetic receptors, as is the case of macrocyclic compounds, molecular imprinted polymers, organometallic cages, among others, to bind amino acids, small peptides and proteins. In this critical review, we present and discuss selected examples of synthetic receptors for amino acids and peptides, with a greater focus on supramolecular receptors, which show great promise for the selective recognition of these biomolecules in physiological conditions. We decided to focus preferentially on small synthetic receptors (leaving out of this review high molecular weight polymeric systems) for which more detailed and accurate molecular level information regarding the main structural and thermodynamic features of the receptor biomolecule assemblies is available.

Acrylamide-hemoglobin adduct: A spectroscopic study.

Acrylamide is a neurotoxic and carcinogenic organic compound that is able to bind to several biomolecules and form adducts, through nucleophilic addition and in vivo by the Maillard Reaction, interfering with the biological functions of these molecules. Hemoglobin is one of the most abundant intracellular blood proteins, and thus it is of high interest to understand whether the binding of acrylamide can alter its properties. The interaction of acrylamide with hemoglobin was assessed in a 20:1 ratio, and after a 72 h-incubation period, a decrease of ca. 50% in the absorbance of the hemoglobin's Soret band was observed at 37 °C. This together with the analysis of circular dichroism spectra indicate that acrylamide binds in close proximity to the heme group. These perturbations were confirmed to not correspond to the loss of the heme group and were mostly reverted after passing the protein through a size-exclusion chromatographic matrix, suggesting a dominant non-covalent interaction for the observed effect. The thermodynamic parameters of unfolding in the absence and presence of acrylamide, suggest an interaction based on H-bonds and van der Waals forces that slightly stabilizes hemoglobin. The oxygen binding capacity of hemoglobin does not seem to be hindered, as no differences in the Q bands were observed in the adduct.