A novel cell-targeting, pH-sensitive polymeric carrier was employed in this study for delivery of the anticancer drug bortezomib (BTZ) to cancer cells. Our strategy is based on facile conjugation of BTZ to catechol-containing polymeric carriers that are designed to be taken up selectively by cancer cells through cell surface receptor-mediated mechanisms. The polymer used as a building block in ...

Poly(ethylene glycol) (PEG) is a highly investigated polymer for the covalent modification of biological macromolecules and surfaces for many pharmaceutical and biotechnical applications. In the modification of biological macromolecules, peptides and proteins are of extreme importance. Reasons for PEGylation (i.e. the covalent attachment of PEG) of peptides and proteins are numerous and include...

Here, we demonstrate that coupling to N-hydroxypropyl methacrylamide (HPMA) copolymer greatly enhances the activity of apoptosis-inducing peptides inside cells. Peptides corresponding to the BH3 domain of Bid were coupled to a thioester-activated HPMA (28.5 kDa) via native chemical ligation in a simple one-pot synthesis. Peptides and polymer conjugates were introduced into cells either by elect...

A model is developed for the mobility of a charge carrier along a conjugated polymer dissolved in solution, as measured by time-resolved microwave conductivity. Each unit cell of the polymer is assigned a torsional degree of freedom, with Brownian dynamics used to include the effects of solvent on the torsions. The barrier to torsional motion is substantially enhanced in the vicinity of the cha...

Polymer conjugates are nano-sized, multi-component constructs already in the clinic as anticancer compounds, both as single agents or as elements of combinations. They have the potential to improve pharmacological therapy of a variety of solid tumors. Polymer-drug conjugation promotes passive tumor targeting by the enhanced permeability and retention (EPR) effect and allows for lysosomotropic d...

Copper-free click chemistry between cyclooctynes and azide is a mild, fast and selective technology for conjugation of oligonucleotides. However, technology for site-specific introduction of the requisite probes by automated protocols is scarce, while the reported cyclooctynes are large and hydrophobic. In this work, it is demonstrated that the introduction of bicyclo[6.1.0]nonyne (BCN) into sy...

The covalent conjugation of large, functionalized molecules remains a frontier in synthetic chemistry, as it requires rapid, chemoselective reactions. The potassium acyltrifluoroborate (KAT)-hydroxylamine amide-forming ligation shows promise for conjugations of biomolecules under aqueous, acidic conditions, but the variants reported to date are not suited to ligations at micromolar concentratio...