Improving the Signal-to-Noise Performance of Molecular Diagnostics with PEG-Lysine Copolymer Dendrons

Abstract

The synthesis, characterization, and use of dendron-like poly(ethylene glycol)-lysine (PEG-Lys) copolymers as an intermediate layer for biomolecular diagnostic signal enhancement is presented. Solid phase Fmoc-peptide synthesis was used to synthesize polymers with one, two, and three PEG-Lys comonomer units in both a linear and first and second-generation dendronic structure directly onto organosilica microspheres. The microsphere surface loadings (number of free amine sites) were modified and quantified through an innovative use of the protecting groups of coupled amino acids. Surfaces with 0.1-100% of the original loading corresponding to 0.3-270 nmol/m2 of free amines were achieved. The influence of polymer structure and surface loading (grafting density) on the signal-to-noise of the microsphere-based molecular diagnostic was assessed measuring the difference in the signal of a model protease digestion assay and reduction in the nonspecific adsorption of bovine serum albumin. Increasing the polymer grafting density and the addition of dendronic branching were both found to increase the assay signal and reduce the nonspecific protein adsorption.

Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives

“…A PEG-poly(lysine) dendron was used as a biocompatible scaffold for biomolecular diagnostic signal enhancement in cancer diagnosis. 135 A PEG-poly(lysine) dendron with cholic acid surface exhibited high biocompatibility (90% cell viability even at a polymer concentration of 2 mg mL À1 , for both normal human fibroblast cells and ES-2 ovarian cancer cells) and paclitaxel loading capacity, and the nanomedicine containing paclitaxel achieved superior in vivo antitumour activity and higher maximum tolerated doses in comparison to free paclitaxel, which is attributed to the EPR effect of the nanoformulations 126 (Fig. 10).…”

Incorporation of Monodisperse Oligoethyleneglycol Amino Acids into Anticonvulsant Analogues of Galanin and Neuropeptide Y Provides Peripherally Acting Analgesics

“…Interestingly, dPEGylation proved useful in the development of peripherally active small molecular drug candidates, such as the naloxol analogue NKTR-118, which is currently under phase III clinical trial to reverse opioid-induced constipation . The dPEGylation was also applied to multimeric conjugates, dendrons, − polymer brushes, , precision polymers, space defined peptide-hydrogels, self-assembling dPEG-peptide conjugates, liposomal drug delivery systems, protein–protein interaction molecular tools, cell-penetrating peptides for cellular uptake mechanism studys and site-specific protein dPEGylation. , …”

Dendritic Molecules on Solid Support: Solid‐Phase Synthesis and Applications

“…16d MAP-like systems can also be used as biomineralization templates, 88 metal ion complexants, 89 protein mimics, 90 and molecular probes for enzymatic activity. 20,91 Argininebearing polylysine dendrons demonstrated strong antiangiogenic activity. 92 Similar arginine-decorated MAP-like polylysines, as well as loligomers, MAP-like dendrons decorated with cytoplasmic translocation signal, and nuclear localization signal peptides, were studied as cell and nucleus membrane translocation agents and vehicles for delivery of exogenous molecules into cells and particular cell compartments.…”