In the groove! A tetracationic supramolecular cylinder, [Fe2L3]4+ (L=C25H20N4), with a triple‐helical architecture is just the right size to fit into the major groove of DNA (see picture) and too big to fit into the minor groove. NMR spectroscopic data confirm that the cylinder binds in the major groove. Linear dichroism shows that very low loadings of [Fe2L3]4+ have a dramatic bending effect on the DNA and atomic force microscopy images show that this is an intramolecular effect resulting in coils of DNA.
We have designed a synthetic tetracationic metallo-supramolecular cylinder that targets the major groove of DNA with a binding constant in excess of 10 7 M ؊1 and induces DNA bending and intramolecular coiling. The two enantiomers of the helical molecule bind differently to DNA and have different structural effects. We report the characterization of the interactions by a range of biophysical techniques. The M helical cylinder binds to the major groove and induces dramatic intramolecular coiling. The DNA bending is less dramatic for the P enantiomer.W hile DNA encodes the essential blueprint for life, within biological systems its structure and function is regulated by proteins. In the postgenomic environment the goal is to understand the processing of the genetic code and how to stimulate or prevent this processing. To achieve this end a variety of different types of molecular tools will be required that recognize the genetic code in a sequence-selective fashion. Within biological systems, sequencespecific code recognition is generally achieved by the surface motifs of proteins, which generally interact noncovalently with the major groove of DNA (1-3). The major groove is particularly attractive for DNA recognition because the size and shape of the major groove of B-DNA varies most with base sequence. For example, transcriptional regulators often involve cylindrical binding units, such as ␣-helices or zinc fingers, that insert into the major groove and may kink the DNA (1-3).Oligonucleotides (synthetic and natural) can selectively recognize DNA by forming triplexes through binding in the major groove (4). Neutral oligonucleotide analogues (e.g., peptide nucleic acids) can achieve similar effects, although more commonly they achieve sequence selectivity through strand displacement (5).Such biomacromolecule recognition of DNA contrasts with synthetic small molecule recognition agents. Synthetic molecules that achieve sequence selectivity include well-known minor groove binders such as amide-linked imidazole͞pyrole oligomers and polymers (6), which in common with many small-molecule DNA-binding agents target the minor groove (7). Alternatively small molecules can act by means of intercalation (8, 9). Synthetic agents that target the major groove of DNA with recognition through noncovalent surface motifs have the potential to be a powerful new tool in the armory of reagents that is being developed to tackle the postgenomic challenge. However, to date little progress has been made in this direction, caused in large part by the size of the molecular surfaces required.DNA binding by metal complexes through formation of metal-ligand bonds (e.g., cisplatin) has been extensively studied and usually focuses on binding to N7 of G and A residues (ref. 10 and references therein). By contrast, noncovalent binding of metal complexes to DNA is a less well-developed area and has primarily centered around approximately spherical ruthenium polypyridyl complexes, complexes bearing planar intercalating units, or combinations thereof ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.