Lexitropsins: rational design of DNA sequence reading agents as novel anti-cancer agents and potential cellular probes.

Alternative approaches to the problem of developing DNA sequence-specific agents for potential use in diagnosis and therapy of cancer are reviewed. The major problems of oligonucleotide probes, i.e. difficulty of cellular uptake and susceptibility to intracellular degradation, suggested as possible alternatives the employment of certain oligopeptide agents. Progress in the development of lexitropsins, or information-reading oligopeptides, which bind selectively to the minor groove of duplex nucleic acids, is discussed. The ability to engineer lexitropsins to recognize and bind to predetermined sequences, the ready cellular uptake and concentration in the cell nucleus may offer advantages in the development of cellular regulatory agents. The anti-cancer efficacy of prototype sequence-specific minor groove alkylators is described.