Advances towards Cell‐Specific Gene Transfection: A Small‐Molecule Approach Allows Order‐of‐Magnitude Selectivity

Abstract

A transfection vector that can home in on tumors is reported. Whereas previous vectors that allow moderately cell selective gene transfection used larger systems, this small‐molecule approach paved the way for precise structure‐activity relationship optimization. For this, biotin, which mediates cell selectivity, was combined with the potent DNA‐binding motif tetralysine‐guanidinocarbonypyrrol via a hydrophilic linker, thus enabling SAR‐based optimization. The new vector mediated biotin receptor (BR)‐selective transfection of cell lines with different BR expression levels. Computer‐based analyses of microscopy images revealed a preference of one order of magnitude for the BR‐positive cell lines over the BR‐negative controls.

Dual activity inhibition of threonine aspartase 1 by a single bisphosphate ligand

“…S2 and Table S1†) utilizing the guanidiniocarbonylpyrrole (GCP) 38 motif introduced by Carsten Schmuck to address surface-accessible glutamate/aspartate residues for different target proteins including Taspase 1, 10,14,35,39–43 and thus significantly advanced its applicability previously focused on gene delivery. 44–53 In particular for Taspase 1, we could rely on the presence of a substantial number of acidic amino acids dispersed on its loop structure in direct vicinity of the NLS (Fig. 1).…”