Hyperbranched polymers containing oxazoline monomers and succinic anhydride: Applications in fast drying,low solvent coating formulations

Melt-polycondensation of succinic acid anhydride with oxazoline-based diol monomers gave hyperbranched polymers with carboxylicacids terminal groups. ¹H NMR and quantitative ¹³C NMR spectroscopy coupled with DEPT-135 ¹³C NMR experiment showed high degrees of branching (over 60%). Esterification of the acid end groups by addition of citronellol at 160 °C produced novel white spirit soluble resins which were characterized by Fourier transform-infrared (FTIR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Blends of the new hyperbranched materials with commercial alkyd resins resulted in a dramatic, concentration dependent drop in viscosity. Solvent-borne coatings were formulated containing the hyperbranched polymers. Dynamic mechanical analysis studies revealed that the air drying rates of the new coating systems were enhanced compared with identical formulations containing only commercial alkyd resins.     

Crystal structures of high affinity human T-cell receptors bound to peptide major histocompatibility complex reveal native diagonal binding geometry

Naturally selected T-cell receptors (TCRs) are characterised by low binding affinities, typically in the range 1-100 microM. Crystal structures of syngeneic TCRs bound to peptide major histocompatibility complex (pMHC) antigens exhibit a conserved mode of binding characterised by a distinct diagonal binding geometry, with poor shape complementarity (SC) between receptor and ligand. Here, we report the structures of three in vitro affinity enhanced TCRs that recognise the pMHC tumour epitope NY-ESO(157-165) (SLLMWITQC). These crystal structures reveal that the docking mode for the high affinity TCRs is identical to that reported for the parental wild-type TCR, with only subtle changes in the mutated complementarity determining regions (CDRs) that form contacts with pMHC; both CDR2 and CDR3 mutations act synergistically to improve the overall affinity. Comparison of free and bound TCR structures for both wild-type and a CDR3 mutant reveal an induced fit mechanism arising from restructuring of CDR3 loops which allows better peptide binding. Overall, an increased interface area, improved SC and additional H-bonding interactions are observed, accounting for the increase in affinity. Most notably, there is a marked increase in the SC for the central methionine and tryptophan peptide motif over the native TCR.     

Stable, soluble T-cell receptor molecules for crystallization and therapeutics

Antibody and T-cell receptors (TCRs) are the primary recognitionmolecules of the adaptive immune system. Antibodies have beenextensively characterized and are being developed for a largenumber of therapeutic applications. This has been possible becauseof the ability to manufacture stable, soluble, monoclonal antibodieswhich retain the antigen specificity of B cells. Unlike antibodies,TCRs are not expressed in a soluble form, but are anchored tothe T-cell surface by an insoluble trans-membrane domain. Characterizationand development of TCRs has been hampered by the lack of suitablemethods for producing them as soluble and stable proteins. Herewe report the engineering of soluble human TCRs suitable forcrystallization studies and potentially for in vivo therapeuticuse. Received March 11, 2003; revised July 1, 2003; accepted July 30, 2003.     

Lightly branched comb polyesters: Application in fast drying solvent-borne coating formulations

Novel oxazoline-based comb-polymers possessing linoleyl or oleic side chains have been synthesized and used to produce low viscosity coatings. Inclusion of the polymers in model paint formulations results in coatings that exhibit faster drying times than commercially available alkyd resin formulations. The comb polymers were produced from diol substituted oxazoline monomers that were synthesized through a scalable, solvent free protocol and purified by simple recrystallisation. Co-polymerisation of the oxazolines with adipic acid at 160 °C in the bulk resulted in the targeted polyester comb type polymers. The polymers were soluble in a range of organic solvents and compatible with commercial alkyd resins. Model paint formulations containing up to 40 wt% of the linoleyl-based comb polymers exhibited a dramatic reduction in viscosity (from 35 to 13 Poise at 25 °C) with increasing quantities of polymer added. Dynamic mechanical analysis (DMA) studies revealed that the drying rate of the model paint formulations containing the comb polymers was enhanced when compared with that of commercial alkyd resins.