Oxidation of tertiary amine-derivatized surfaces to control protein adhesion

Selective oxidation of omega-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them. Efficient preparation of both secondary and tertiary linker amides as judged by X-ray photoelectron spectroscopy (XPS) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance (QCM) sensors using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl hexafluorophosphate methanaminium uronium (HATU). Oxidation with hydrogen peroxide was similarly assessed, and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM. Tertiary amine-functionalized sensors adsorbed multilayers of aggregated lysozyme, whereas tertiary amine N-oxides and triethylene glycol-terminated monolayers are consistent with small protein aggregates. The surface containing a dimethylamine N-oxide headgroup and ethyl secondary amide linker showed the largest difference in adsorption of both proteins. Oxidation of tertiary amine decorated surfaces therefore holds the potential for selective deposition of proteins and cells through masking and other patterning techniques

Absolut “copper catalyzation perfected”; robust living polymerization of NIPAM : Guinness is good for SET-LRP

The controlled polymerization of N-isopropyl acrylamide (NIPAM) is reported in a range of international beers, wine, ciders and spirits utilizing Cu(0)-mediated living radical polymerization (SET-LRP). Highly active Cu(0) is first formed in situ by the rapid disproportionation of [Cu(I)(Me6-Tren)Br] in the commercial water–alcohol mixtures. Rapid, yet highly controlled, radical polymerization follows (Đ values as low as 1.05) despite the numerous chemicals of diverse functionality present in these solvents e.g. alpha acids, sugars, phenols, terpenoids, flavonoids, tannins, metallo-complexes, anethole etc. The results herein demonstrate the robust nature of the aqueous SET-LRP protocol, underlining its ability to operate efficiently in a wide range of complex chemical environments

Glycopolymers via catalytic chain transfer polymerisation (CCTP), Huisgens cycloaddition and thiol–ene double click reactions

CCTP has been used to give alkyne-functional macromonomers which are subsequently functionalised with sugar azides and thiols, using both CuAAC and thiol-ene Michael addition reactions, to yield end-functionalised glycopolymers in a convenient manner

Glycopolymers via catalytic chain transfer polymerisation (CCTP), Huisgens cycloaddition and thiol–ene double click reactions

CCTP has been used to give alkyne-functional macromonomers which are subsequently functionalised with sugar azides and thiols, using both CuAAC and thiol-ene Michael addition reactions, to yield end-functionalised glycopolymers in a convenient manner

POLY 433-site-specific conjugation of a well-defined functional poly(mPEG1100) methacrylate to salmon calcitonin : design, synthesis, characterization and investigation via NMR

The therapeutic value and nature of bio-molecules has been identified and exploited in numerous ways for several years. Conjugation of bio-molecules with synthetic molecules/macromolecules is one method of extending their lifetime by inhibiting degradation and excretion from the body to enhance therapeutic activity. One such technique is ‘pegylation' a term which refers to the combination of functionalized poly(ethylene glycol) with an appropriate bio-molecule. Commercially available, PEGylated drugs are in some cases a mixture of different positional isomers, the development of further generations of polymer therapeutic requires the design of site-specific conjugation strategies. Knowledge of the site of attachment will ensure both conjugation reproducibility and a better understanding of the bioconjugate structure/activity relationship. In this present work, the possibility of employing such end functional macromolecules for the targeting of the N-terminus of a biologically relevant peptide, salmon calcitonin was explored. The resultant polymer bio-conjugate was investigated by NMR and biological assays

Site-specific N-terminus conjugation of poly(mPEG(1100)) methacrylates to salmon calcitonin : synthesis and preliminary biological evaluation

Recent advances in polymerization strategies have led to the development of novel polymer (poly) peptide biohybrid materials with potential application in the field of macromolecular therapeutics. In this current work, comb-shaped alpha-aldehyde poly(monomethoxy polyethylene glycol)methacrylates (p(mPEG)MA) with molecular masses in the 6.5-109 kDa range were prepared and conjugated, via reductive amination, to the Cys1 N-terminus of salmon calcitonin (sCT), a calcitropic hormone currently administered for the treatment of a number of hypercalcaemia-related diseases. The conjugation site was determined by tryptic digestion of the sCT-p(mPEG(1100)) MA biohybrids in conjunction with LC-MS MALDI-TOF spectrometry. Preliminary in vitro biological tests show that the polymer conjugation does not interfere with the biological activity of the sCT

Psychology in Administration: A Research Orientation, par T.W. Costello et S.S. Zalkin, Prentice-Hall, Inc., Englewood Cliffs, N.J., 1963. 500 pages.

Selective oxidation of ω-tertiary amine self-assembled thiol monolayers to tertiary amine <i>N</i>-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them. Efficient preparation of both secondary and tertiary linker amides as judged by X-ray photoelectron spectroscopy (XPS) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance (QCM) sensors using 2-(1<i>H</i>-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl hexafluorophosphate methanaminium uronium (HATU). Oxidation with hydrogen peroxide was similarly assessed, and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM. Tertiary amine-functionalized sensors adsorbed multilayers of aggregated lysozyme, whereas tertiary amine <i>N</i>-oxides and triethylene glycol-terminated monolayers are consistent with small protein aggregates. The surface containing a dimethylamine <i>N</i>-oxide headgroup and ethyl secondary amide linker showed the largest difference in adsorption of both proteins. Oxidation of tertiary amine decorated surfaces therefore holds the potential for selective deposition of proteins and cells through masking and other patterning techniques

Absolut “copper catalyzation perfected”; robust living polymerization of NIPAM: Guinness is good for SET-LRP

The controlled polymerization of N-isopropyl acrylamide (NIPAM) is reported in a range of international beers, wine, ciders and spirits utilizing Cu(0)-mediated living radical polymerization (SET-LRP). Highly active Cu(0) is first formed in situ by the rapid disproportionation of [Cu(I)(Me6-Tren)Br] in the commercial water–alcohol mixtures. Rapid, yet highly controlled, radical polymerization follows (Đ values as low as 1.05) despite the numerous chemicals of diverse functionality present in these solvents e.g. alpha acids, sugars, phenols, terpenoids, flavonoids, tannins, metallo-complexes, anethole etc. The results herein demonstrate the robust nature of the aqueous SET-LRP protocol, underlining its ability to operate efficiently in a wide range of complex chemical environments.ISSN:1759-9962ISSN:1759-995

Investigation into thiol-(meth)acrylate Michael addition reactions using amine and phosphine catalysts

This work describes a study into thiol-ene based Michael addition reactions. Different catalysts, primary and tertiary amines and phosphines, were investigated for the reaction of a range of thiols with dimers and oligomers of some (meth)acrylates. Primary and tertiary amines are efficient catalysts for the thiol-ene reaction, although these catalysts require several hours to reach high conversion. Moreover, the phosphine catalysts, dimethylphenylphosphine (DMPP) and tris-(2-carboxyethyl)phosphine (TCEP), were investigated in detail. DMPP is an efficacious catalyst yielding complete conversion in few minutes under optimized conditions. Importantly, the concentration of DMPP should be kept at catalytic levels to avoid the formation of by-products, originating from the addition of DMPP to the vinyl group. Furthermore, TCEP is an efficient catalyst for thiol-ene reactions in aqueous media when the pH of the medium is higher than 8.0 since at acidic pH the formation of by-products is observed