A 1 : 2 copper(II)-tripeptide complex for DNA binding and cleavage agent under physiological conditions

A 1 : 2 copper-tripeptide complex, [CuII(Boc-His-Gly-His-OMe)2]2+, was synthesized and structurally characterized. The absorption band at 577 nm suggests a square-planar geometry around CuII. The DNA-binding and DNA-cleavage properties of the CuII complex were investigated. The complex binds to calf thymus DNA (CT DNA) in an intercalative fashion and cleaves plasmid pUC-19 DNA hydrolytically at micromolar concentrations under physiological conditions. The intrinsic binding constant (Kb = 1.2×102 M-1) for the binding of Cu-tripeptide complex with DNA suggests that this complex is suitable for rapid diffusion on the pharmacological time scale

A new S<SUB>4</SUB>-ligated zinc-peptide 1 : 2 complex for the hydrolytic cleavage of DNA

A new sulfur-ligated Zn-peptide 1 : 2 complex, [ZnII(Boc-NH-Cys-Gly-Cys-OMe)2]2- (2), was prepared, characterized, and tested for its DNA-binding and -cleavage properties. Complex 2 was found to cleave DNA hydrolytically. The negative charge in 2 reduces the affinity of the complex for DNA, and enhances its binding specificity

Ionpair-pi interactions favor cell penetration of arginine/tryptophan-rich cell-penetrating peptides

Cell-penetrating peptides (CPPs) internalization occurs both by endocytosis and direct translocation through the cell membrane. These different entry routes suggest that molecular partners at the plasma membrane, phospholipids or glycosaminoglycans (GAGs), bind CPPs with different affinity or selectivity. The analysis of sequence-dependent interactions of CPPs with lipids and GAGs should lead to a better understanding of the molecular mechanisms underlying their internalization. CPPs are short sequences generally containing a high number of basic arginines and lysines and sometimes aromatic residues, in particular tryptophans. Tryptophans are crucial residues in membrane-active peptides, because they are important for membrane interaction. Membrane-active peptides often present facial amphiphilicity, which also promote the interaction with lipid bilayers. To study the role of Trp and facial amphiphilicity in cell interaction and penetration of CPPs, a nonapeptide series containing only Arg, Trp or D-Trp residues at different positions was designed. Our quantitative study indicates that to maintain/increase the uptake efficiency, Arg can be advantageously replaced by Trp in the nonapeptides. The presence of Trp in oligoarginines increases the uptake in cells expressing GAGs at their surface, while it compensates for the loss of charge interactions from Arg and maintains similar peptide uptake in GAG-deficient cells. In addition, we show that facial amphiphilicity is not required for efficient uptake of these nonapeptides. Thermodynamic analyses point towards a key role of Trp that highly contributes to the binding enthalpy of complexes formation. Density functional theory (DFT) analysis highlights that salt bridge-pi interactions play a crucial role for the GAG-dependent entry mechanisms