François Otis

Laval University | ULAVAL · Department of Chemistry

Light absorption by rhodopsin leads to the release of all-trans retinal (ATRal) in the lipid phase of photoreceptor disc membranes. Retinol dehydrogenase 8 (RDH8) then reduces ATRal into all-trans retinol, which is the first step of the visual cycle. The membrane binding of RDH8 has been postulated to be mediated by one or more palmitoylated cystei...

A simple model of an uncharged antimicrobial peptide, carrying four crown ether side chains, is modified further by the selective incorporation of arginine side chains to control its secondary structure and its interaction with model membranes and living cells. Conformational studies show that shifting the position of a cationic residue in the pept...

Phosphotyrosine (pTyr) signaling has evolved into a key cell-to-cell communication system. Activated receptor tyrosine kinases (RTKs) initiate several pTyr-dependent signaling networks by creating the docking sites required for the assembly of protein complexes. However, the mechanisms leading to network disassembly and its consequence on signal tr...

Fluorinated peptides attract much interest in the biomedical area because they generally exhibit an enhanced stability compared to their hydrogenated counterparts and because fluorine atoms represent efficient probes to investigate peptide assemblies, especially in membranes. We previously designed and characterized a fluorinated peptide intended t...

A novel 21-residue peptide incorporating six fluorinated amino acids was prepared. It was designed to fold into an amphiphilic alpha helical structure of nanoscale length with one hydrophobic face and one fluorinated face. The formation of a fluorous interface serves as the main vector for the formation of a superstructure in a bilayer membrane. Fl...

FTIR of LX2 in HFIP. (TIF)

Ion transport for sodium salts at a constant concentration of 100 nM of LX2. (TIF)

Topology and parameters of the trifluoromethylated alanine. (PDF)

Calcein release at various concentrations of LX2. (TIF)

Parametrization of the trifluoromethylated alanine. (PDF)

Glutaminyl-tRNAGln in Helicobacter pylori is formed by an indirect route requiring a non-canonical glutamyl-tRNA synthetase and a tRNA-dependent heterotrimeric amidotransferase (AdT) GatCAB. Widespread use of this pathway among prominent human pathogens, and its absence in the mammalian cytoplasm, identify AdT as a target for the development of ant...

Ion channel proteins are complex architectures vital for numerous physiological processes and involved in many diseases. With the aim of developing simpler supramolecular systems mimicking ion transport properties of channel proteins, we will describe novel helical peptides designed to self assemble in membranes into well defined superstructures ca...

We report a practical synthesis of N-Fmoc protected l-fluoroalanine 6 from l-serine. The key step involves a deoxofluorination reaction which was best achieved using XtalFluor-E in the presence of triethylamine trihydrofluoride. We also report the use of 6 in solid-phase peptide synthesis for the preparation of a model tripeptide demonstrating the...

Oriented circular dichroism was used to study the alignment crown ether-modified peptides. The influence of different N- and C- functionalities was assessed using at variable peptide:lipid ratios from 1:20 to 1:200. Neither the functionalities nor the concentration had any major effect on the orientation. The alignment of the 21-mer peptides was al...

Natural ion channel proteins possess remarkable properties that researchers could exploit to develop nanochemotherapeutics and diagnostic devices. Unfortunately, the poor stability, limited availability, and complexity of these structures have precluded their use in practical devices. One solution to these limitations is to develop simpler molecula...

We have prepared fluorescent analogs of known ion-channel-forming synthetic peptide nanostructures. These analogs were designed as probes to gain insight about the mechanism by which self-assembling amphiphilic peptides interact with lipid membranes. Conformational studies demonstrated that the labeled analogs retain their propensity to adopt a str...

We achieved the synthesis of a derivative of phenylalanine with a diazamacrocycle on its side chain by macrocyclization of a dichloride on l-DOPA. We also report its incorporation into peptide structures by solid phase peptide synthesis which will lead to the development of artificial anion channels.

Analogues of a synthetic ion channel made from a helical peptide were used to study the mechanism of cation translocation within bilayer membranes. Derivatives bearing two, three, four, and six crown ethers used as ion relays were synthesized, and their transport abilities across lipid bilayers were measured. The results showed that the maximum dis...

We present experimental data that demonstrate the potential of synthetic crown ether modified peptide nanostructures to act as selective and efficient chemotherapeutic agents that operate by attacking and destroying cell membranes.

We have investigated the interactions between synthetic amphipathic peptides and zwitterionic model membranes. Peptides with 14 and 21 amino acids composed of leucines and phenylalanines modified by the addition of crown ethers have been synthesized. The 14-mer and 21-mer peptides both possess a helical amphipathic structure as revealed by circular...

Toward developing nanostructures for single molecule detection, we report the synthesis of new derivatives of artificial devices that possess ion channel activity. The membrane stability and the ion transport ability of these multiple crown α-helical peptides have been optimized by modulating the polarity of N- and C-terminal groups with incorporat...

We report the design and the synthesis of membrane-active peptide nanostructures, as well as their use as signal transducer in a fluorimetric assay for biologically relevant analytes. Addition of hydrophobic 21-residue peptides bearing six crown ether side chains to a solution of small unilamellar vesicles loaded with a pH-sensitive fluorophore ind...

We report the synthesis and the functional studies of multiple crown alpha-helical peptides designed to form artificial ion channels. The approach combines the versatility of solid phase peptide synthesis, the conformational predictability of peptidic molecules, and the solution synthesis of crown ethers with engineerable ion-binding abilities. Sev...