Multivalent Elastin-Like Glycopolypeptides: Subtle Chemical Structure Modifications with High Impact on Lectin Binding Affinity

A library of synthetic elastin-like glycopolypeptides were synthesized and screened by microscale thermophoresis to identify key structural parameters affecting lectin binding efficacy. While polypeptide backbone size and glycovalency were found to have little influence, the presence of a linker at the anomeric position of galactose and the absence of positive charge on the polypeptide residue holding the sugar unit were found to be critical for the binding to RCA120.Développement de squelettes polypeptidiques recombinants pour la synthèse de glycoconjugués multivalents parfaitement défini

Synthesis, self-assembly, and immunological activity of α-galactose-functionalized dendron–lipid amphiphiles

Nanoassemblies presenting multivalent displays of biologically active carbohydrates are of significant interest for a wide array of biomedical applications ranging from drug delivery to immunotherapy. In this study, glycodendron–lipid hybrids were developed as a new and tunable class of dendritic amphiphiles. A modular synthesis was used to prepare dendron–lipid hybrids comprising distearylglycerol and 0 through 4th generation polyester dendrons with peripheral protected amines. Following deprotection of the amines, an isothiocyanate derivative of C-linked α-galactose (α-Gal) was conjugated to the dendron peripheries, affording amphiphiles with 1 to 16 α-Gal moieties. Self-assembly in water through a solvent exchange process resulted in vesicles for the 0 through 2nd generation systems and micelles for the 3rd and 4th generation systems. The critical aggregation concentrations decreased with increasing dendron generation, suggesting that the effects of increasing molar mass dominated over the effects of increasing the hydrophilic weight fraction. The binding of the assemblies to Griffonia simplicifolia Lectin I (GSL 1), a protein with specificity for α-Gal was studied by quantifying the binding of fluorescently labeled assemblies to GSL 1-coated beads. It was found that binding was enhanced for amphiphiles containing higher generation dendrons. Despite their substantial structural differences with the natural ligands for the CD1d receptor, the glycodendron–lipid hybrids were capable of stimulating invariant natural killer T (iNKT) cells, a class of innate-like T cells that recognize lipid and glycolipid antigens presented by CD1d and that are implicated in a wide range of diseases and conditions including but not limited to infectious diseases, diabetes and cancer

Supramolecular materials via block copolymer self-assembly

This review discusses the potential of block copolymer type macromolecular building blocks for the preparation of self-assembled materials. Three different classes of block copolymer type architectures will be distinguished: i) coil-coil diblock copolymers, ii) rod-coil diblock copolymers, and iii) rod-coil diblock oligomers. The basic principles that underlie the self-assembly of each of these different building blocks will be discussed. These theoretical considerations are complemented with examples from recent literature that illustrate the potential of the different type of block copolymers to prepare (functional) supramolecular materials. Finally, several strategies will be presented that could allow the preparation of stimuli-sensitive self-assembled materials, i.e., materials whose properties can be reversibly manipulated under the action of appropriate external stimuli

Molecular dynamics simulations of side chain liquid crystal polymer molecules in isotropic and liquid-crystalline melts

A detailed molecular dynamics simulation study is described for a polysiloxane side chain liquid crystal polymer (SCLCP). The simulations use a coarse-grained model composed of a combination of isotropic and anisotropic interaction sites. On cooling from a fully isotropic polymer melt, we see spontaneous microphase separation into polymer-rich and mesogen-rich regions. Upon application of a small aligning potential during cooling, the structures that form on microphase separation anneal to produce a smectic-A phase in which the polymer backbone is largely confined between the smectic layers. Several independent quenches from the melt are described that vary in the strength of the aligning potential and the degree of cooling. In each quench, defects were found where the backbone chains hop from one backbone-rich region to the next by tunneling through the mesogenic layers. As expected, the number of such defects is found to depend strongly on the rate of cooling. In the vicinity of such a defect, the smectic-A structure of the mesogen-rich layers is disrupted to give nematiclike ordering. Additionally, several extensive annealing runs of approximately 40 ns duration have been carried out at the point of microphase separation. During annealing the polymer backbone is seen to be slowly excluded from the mesogenic layers and lie perpendicular to the smectic-A director. These observations agree with previous assumptions about the structure of a SCLCP and with interpretations of x-ray diffraction and small angle neutron scattering data. The flexible alkyl spacers, which link the backbone to the mesogens, are found to form sublayers around the backbone layer

Strong anisotropic nematic order in liquid crystal polymers: a quasi-elastic neutron scattering study

From quasi-elastic neutron scattering experiments performed in glassy, nematic and isotropic phases, the dynamics of oriented samples of strong anisotropic side-on fixed liquid crystal polymers have been analysed. Using the selective deuteration method, we are able to attribute motions to specific parts of the molecule in the parallel and perpendicular orientations. The motions of the whole macromolecule decrease as soon as the temperature decreases below the isotropic-nematic transition. Nevertheless, the motions of the polymer backbone, compared to the whole polymer dynamics, are systematically reduced, even in the isotropic phase. Moreover, an anisotropy of the motions is revealed, with a reduction in the direction parallel to the orientation. An harmonic character of the vibrational processes is also evidenced. We conclude that the anisotropy of the dynamic corroborates the anisotropy of conformation of the macromolecule (so-called jacketed structure)