Utilizing Combinatorial Chemistry and Rational Design: Peptidic Tweezers with Nanomolar Affinity to DNA Can Be Transformed into Efficient Vectors for Gene Delivery by Addition of a Lipophilic Tail

Into the library: Screening a focused library of 259 peptide tweezers, composed of two identical arms with zero to three amino acids and an artificial anion recognition site, yielded DNA binders with nanomolar affinity. These ligands are only modest gene carriers (transfection efficiency <10 %); however, excellent transfection efficiencies (up to 90 %) were achieved after the covalent attachment of long aliphatic chains.