Nicolas Spinelli

High affinity glycodendrimers for the lectin LecB from Pseudomonas aeruginosa.

Following an iterative oxime ligation procedure, cyclopeptide (R) and lysine-based dendron (D) were combined in all possible arrangements and successively functionalized with α-fucose and β-fucose to provide a new series of hexadecavalent glycosylated scaffolds (i.e., scaffolds RD16, RR16, DR16, and DD16). These compounds and smaller analogs (tetra- and hexavalent scaffolds R4 and R6) were used to evaluate the influence of the ligand valency and architecture, and of the anomer configuration in the binding to the αFuc-specific lectin LecB from Pseudomonas aeruginosa . Competitive enzyme-linked lectin assays (ELLA) revealed that only the RD16 architecture displaying αFuc (9A) reaches strong binding improvement (IC50 of 0.6 nM) over αMeFuc, and increases the α-selectivity of LecB. Dissociation constant of 28 nM was measured by isothermal titration micorcalorimetry (ITC) for 9A, which represents the highest affinity ligand ever reported for LecB. ITC and molecular modeling suggested that the high affinity observed might be due to an aggregative chelate binding involving four sugar head groups and two lectins. Interestingly, unprecedented binding effects were observed with β-fucosylated conjugates, albeit being less active than the corresponding ligands of the αFuc series. In particular, the more flexible lysine-based dendritic structures (15B and 18B) showed a slight inhibitory enhancement in comparison with those having cyclopeptide core.

Use of Allylic Protecting Groups for the Synthesis of Base‐Sensitive Prooligonucleotides

The synthesis of mixed MeSATE-phosphotriester and -phosphodiester prooligonucleotides [MeSATE = 2-(acetylthio)ethyl] of various sequences is described. The strategy is based on the use of allyloxycarbonyl (AOC) protection for nucleobases and MeSATE and allyl (All) protection for internucleosidic phosphates, in combination with palladium(0) deprotection. The synthesis was achieved by the use of phosphoramidite chemistry on a photolabile solid support, enabling MALDI-TOF mass spectrometric analysis to be performed on the still anchored prooligonucleotides

Molecular engineering of biomolecules for nanobio-sciences

Biologically programmed molecular recognition provides the basis of all natural systems and supplies evolution optimised functional materials from self-assembly of a limited number of molecular building blocks. Biomolecules such as peptides, nucleic acids and carbohydrates represent a diverse supply of structural building blocks for the chemist to design and fabricate new functional nanostructured architectures. In this context, we review here the chemistry part of our Nanobio program, we have developed in Grenoble to manipulate such biomolecules, and organic molecules, as well as assemble combinations thereof using a template assembled approach. With this methodology, we have prepared new integrated functional systems exhibiting designed properties in the field of nanovectors, biosensors as well as controlled peptide self-assembly. Thus this molecular engineering approach allows for the rational design of systems with integrated tailor-made properties and paves the way to more elaborate applications by bottom-up design in the domain of nanobiosciences.

Analysis of solid-supported oligonucleotides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

This study presents matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) as a powerful tool to analyze and characterize oligonucleotides covalently linked to a solid support during their synthesis. The analysis of the fragment ions generated either in negative or positive mode allows direct and easy access to the nucleotide sequence and identification of the internucleosidic linkage. The mechanisms of the fragmentation of the solid-supported oligonucleotides induced by MALDI-TOFMS are discussed. Copyright 2000 John Wiley & Sons, Ltd.

Pro-oligonucleotide synthesis using allyl and allyloxycarbonyl protections: direct MALDI-TOF MS analysis on solid support.

The solid-support synthesis of pro-oligonucleotide heteropolymer chimeras had been performed with allyloxycarbonyl group (AOC) for the protection of nucleobases and of allyl and S-acetyl-2-thioethyl (MeSATE) for phosphate protections to respectively generate phosphodiester and MeSATE phosphotriester linkages.

Direct MALDI-TOF MS analysis of oligonucleotides on solid support through a photolabile linker.

MALDI-TOF mass spectrometry was used to analyze oligonucleotides still anchored to long-chain alkylamine controlled-pore glass (LCAA-CPG) through a photolabile linker. This technique is useful to follow supported chemical reactions in real time and monitor by-products formation.