Intramolecular DNA coiling mediated by metallo-supramolecular cylinders: Differential binding of P and M helical enantiomers

Abstract

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 ...

Recognition of DNA bulges by dinuclear iron(II) metallosupramolecular helicates

“…To confirm that the helicates were not degraded at elevated temperatures during the DNA melting experiments, the absorbance at 575 nm (metal-to-ligand charge transfer band) [20,25] 4+ helicates used in the DNA melting experiments had a negligible effect on the thermal stability of the duplexes containing bulges. Concentrations of these salts~1000-fold higher than the concentrations of the [Fe 2 L 3 ] 4+ helicates used in the DNA melting experiments described in the present work had to be used to obtain even a small amount of thermal stabilization (by~2-3°C) of the duplexes containing bulges.…”

“…1) has been described previously [19,25,41,42]. Enantiomerically pure material was obtained by use of a cellulose column (~20 lM; Sigma-Aldrich) and elution with aqueous NaCl (20 mM) [43].…”

“…[Fe 2 L 3 ] 4+ is synthesized as a mixture of two enantiomers (M and P, denoting left-handed or minus and right-handed or plus helical twists), which have different structural effects on DNA [20,25] 4+ to unusual DNA structures (three-way junctions and G-quadruplexes), the enantiomers can recognize some DNA bulges.…”

Progress in Helicates Directed by Metal Coordination

“…螺旋分子的两种对映异构体采 用不同的方式与 DNA 进行结合, M 型筒状螺旋与 DNA 的大沟结合诱导其发生分子内的卷曲, P 型螺旋跨越两 个磷酸骨架与小沟结合在一起, 引起 DNA 发生不太明 显的弯曲 [64] . 作者进一步研究发现筒状结构还可以识…”

Selective and Sensitive Detection of Silver(I) Ion Based on Tetracationic Complex and TGA/GSH Co-capped Quantum Dots as an Effective Fluorescent Sensing Platform

“…We used thioglycolic acid ≥98%, glutathione 98%, CdCl2·2.5H2O 99.99%, K2TeO3 99.5%, and NaBH4 ≥98%. [Fe2L3] 4+ (L = 4,4′-methylenebis[N-(2-pyridinylmethylene)benzenamine) was synthesized according to methods in the literature 21 (Scheme S1, Supporting Information). All other chemicals were of analytical reagent grade and used as received.…”