Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti- Drug Delivery Systems.

Two series of new hybrid γ/γ-peptides, γ-CC and γ-CT, formed by (1,2)-3-amino-2,2,dimethylcyclobutane-1-carboxylic acid joined in alternation to a -functionalized - or -γ-amino-l-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti- drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both γ-CC and γ-CT tetradecamers were microbicidal on the protozoan parasite beyond 25 μM, with significant intracellular accumulation.