Current Medicinal Chemistry - Volume 8, Issue 5, 2001

DNA is a well characterized intracellular target but its large size and sequential nature make it an elusive target for selective drug action. Binding of low molecular weight ligands to DNA causes a wide variety of potential biological responses. In this respect the main consideration is given to recent developments in DNA sequence selective binding agents bearing conjugated effectors because of their potential application in di Read More

Lexitropsins are modular polyamide molecules that are designed to read the base sequence of DNA. Lexitropsins constructed of three types of subunits-pyrrole, imidazole and hydroxypyrrole-allow full recognition of DNA base sequences. Structural studies have revealed the atomic basis of this specificity. Theoretical studies have explored the effectiveness of lexitropsins in targeting a given sequence within a genome, and ha Read More

More and more, nucleic acids have become prime targets in the development of new compounds, able to control gene expression. For the development of new sequence selective dsDNA binding ligands, one can learn a lot from existing models such as, lexitropsins, combilexins and actinomycin D. This analysis, together with the knowledge of the details on protein-DNA interactions, has inspired the assembly of unnat Read More

Recent work on a number of different classes of anticancer agents that alkylate DNA in the minor groove is reviewed. There has been much work with nitrogen mustards, where attachment of the mustard unit to carrier molecules can change the normal patterns of both regio- and sequence-selectivity, from reaction primarily at most guanine N7 sites in the major groove to a few adenine N3 sites at the 3-end of poly(A(slash)T Read More

PNA (peptide nucleic acid) is a DNA mimic with a pseudopeptide (polyamide) backbone which can be used to target double stranded DNA with high sequence specificity. PNA therefore has great potential in the development of biomolecular tools for manipulation of DNA as well as for the development of DNA targeted gene therapeutic drugs. The status of this field is discussed in terms of PNA binding modes and mechanis Read More

The last few years have represented an accelerated accumulation in detailed information about ligand-DNA interactions. A collected view of literature information is essential for advancing our understanding of the principles of ligand-DNA recognition, utilizing this valuable information for construction of a modeling database, and eventually the rational design of DNA-binding ligands possessing desired properties. This revie Read More