Recognition of RNA duplex by a neomycin-Hoechst 33258 conjugate.

DNA minor groove binding drugs such as Hoechst 33258 have been shown to bind to a number of RNA structures. Similarly, RNA binding ligands such as neomycin have been shown by us to bind to a number of A-form DNA structures. A neomycin-Hoechst 33258 conjugate was recently shown to bind B-DNA, where Hoechst exhibits high affinity for the minor groove of A/T tract DNA and neomycin docks into the major groove.

Symptomatic relief of botulinum neurotoxin/a intoxication with aminopyridines: a new twist on an old molecule.

Botulinum neurotoxins (BoNT) are the etiological agents responsible for botulism, a disease characterized by peripheral neuromuscular blockade and a characteristic flaccid paralysis of humans. BoNT/A is the most toxic protein known to man and has been classified by the Centers of Disease Control (CDC) as one of the six highest-risk threat agents for bioterrorism. Of particular concern is the apparent lack of clinical interventions that can reverse cellular intoxication.

Triple recognition of B-DNA by a neomycin-Hoechst 33258-pyrene conjugate.

Recent developments have indicated that aminoglycoside binding is not limited to RNA, but to nucleic acids that, like RNA, adopt conformations similar to its A-form. We further sought to expand the utility of aminoglycoside binding to B-DNA structures by conjugating neomycin, an aminoglycoside antibiotic, with the B-DNA minor groove binding ligand Hoechst 33258. Envisioning a dual groove binding mode, we have extended the potential recognition process to include a third, intercalative moiety.

Triple recognition of B-DNA.

A novel conjugate of Hoechst 33258, pyrene and neomycin was synthesized and examined for its binding and stabilization of A-T rich DNA duplexes using spectroscopic and viscometric techniques. The conjugate, containing three well known ligands that bind nucleic acids albeit in different binding modes, was found to significantly stabilize DNA over parent conjugates containing only one or both of the other recognition elements. The study represents the first example of DNA molecular recognition capable of minor/major groove recognition in conjunction with intercalation.

The strange case of the botulinum neurotoxin: using chemistry and biology to modulate the most deadly poison.

In the classic novella "The Strange Case of Dr. Jekyll and Mr. Hyde", Robert Louis Stevenson paints a stark picture of the duality of good and evil within a single man.

Biologically templated organic polymers with nanoscale order.

Methods for the construction of ordered nanoscale arrays have been implicated in fields ranging from separation technologies to microelectronics. Yet, despite the plethora of nanoscale structures assembled in nature that use a templating strategy, chemists have been unable to replicate this success. A technology is reported for templated organic polymers composed of filamentous bacteriophage-polyacrylamide biomacromolecules that self-assemble into highly ordered helical bundles displaying hexagonal close packing.

Recognition of B-DNA by neomycin--Hoechst 33258 conjugates.

Recent developments have indicated that aminoglycoside binding is limited not to RNA but to nucleic acids that, like RNA, adopt conformations similar to the A-form. We have further sought to expand the utility of aminoglycoside binding to B-DNA structures by conjugating neomycin, an aminoglycoside antibiotic, with the B-DNA minor groove binding ligand Hoechst 33258. Described herein are novel neomycin-Hoechst 33258 conjugates developed for exploring B-DNA groove recognition.

Reaching into the major groove of B-DNA: synthesis and nucleic acid binding of a neomycin-hoechst 33258 conjugate.

Synthesis of a neomycin-Hoechst 33258 conjugate is reported. The conjugate combines the ligands known to selectively bind in the duplex and the triplex groove. The conjugate stabilizes DNA duplex over DNA triplex.

Aminoglycoside (neomycin) preference is for A-form nucleic acids, not just RNA: results from a competition dialysis study.

Aminoglycosides have been at the forefront of antimicrobial therapy for the past 50 years. Their specificity is believed to lie in binding duplex RNAs (rRNA). Competition dialysis studies of various nucleic acid forms with 9-aminoacridine, quinacrine, and a neomycin-acridine conjugate were carried out.

Particle beam glow discharge mass spectrometry: spectral characteristics of nucleobases.

Use of a particle beam glow discharge (PB-GD) source for mass spectrometric determinations of deoxy- and ribonucleosides and nucleotides is described. Use of this combination of sample introduction and ion source decouples the vaporization and ionization steps, leading to very simple spectral structure. The mass spectra of these compounds are EI-like in nature, with clearly identified molecular ions and fragmentation patterns that are easily rationalized.

Neomycin binding to Watson-Hoogsteen (W-H) DNA triplex groove: a model.

Neomycin is the most effective aminoglycoside (groove binder) in stabilizing a DNA triple helix. It stabilizes TAT, as well as mixed base DNA triplexes, better than known DNA minor groove binders (which usually destabilize the triplex) and polyamines. Neomycin selectively stabilizes the triplex (in the presence of salt), without any effect on the DNA duplex.