Courtney L. Sherman

ESI-MS characterization of a novel pyrrole-inosine nucleoside that interacts with guanine bases.

Based on binding studies undertaken by electrospray ionization-mass spectrometry, a synthetic pyrrole-inosine nucleoside, 1, capable of forming an extended three-point Hoogsteen-type hydrogen-bonding interaction with guanine, is shown to form specific complexes with two different quadruplex DNA structures [dTG(4)T](4) and d(T(2)G(4))(4) as well as guanine-rich duplex DNA. The binding interactions of two other analogs were evaluated in order to unravel the structural features that contribute to specific DNA recognition. The importance of the Hoogsteen interactions was confirmed through the absence of specific binding when the pyrrole NH hydrogen-bonding site was blocked or removed. While 2, with a large blocking group, was not found to interact with virtually any form of DNA, 3, with the pyrrole functionality missing, was found to interact non-specifically with several types of DNA. The specific binding of 1 to guanine-rich DNA emphasizes the necessity of careful ligand design for specific sequence recognition.

Identification of the adduct between a 4-aza-3-ene-1,6-diyne and DNA using electrospray ionization mass spectrometry

The interactions between a novel enediyne [1-methyl-2-(phenylethynyl)-3-(3-phenylprop-2-ynyl)-3H-benzimidazolium] (1) and various cytosine-containing oligonucleotides were studied using electrospray ionization mass spectrometry (ESI-MS) in a flow injection analysis mode useful for small volumes. This enediyne ligand, developed as a potential alternative to the highly cytotoxic natural enediynes, some of which have been successfully used as anti-tumor agents, has previously been shown to interact with DNA through frank strand scission as well as via the formation of adducts that lead to 2′-deoxycytidine-specific cleavage. Through ESI-MS, the structures of these adducts were examined and a sequence dependence of the 2′-deoxycytidine-specific cleavage was noted. Collisionally activated dissociation of the observed adducts confirmed the strength of the interactions between the enediyne and DNA and supports a direct linkage between the enediyne and the cytosine nucleobase, likely the result of a nucleophilic attack of the phenylethynyl group by the cytosine amine.

Electrospray ionization mass spectrometric study of the metal cation complexation capabilities of a novel, doubly cage-annulated molecular box

An unusual molecular box, 4, obtained as a mixture of diastereoisomeric, doubly cage-annulated host molecules, i.e., 4a and 4b, has been prepared. The metal cation complexation properties of the mixture of 4a and 4b thereby obtained have been assessed, with comparison to another bis crown 2, via application of electrospray ionization mass spectrometric (ESI-MS) methods. Both host systems 2 and 4 bind selectively to Li + and Na + , thereby demonstrating preference over the other larger alkali metals. Addition of Ag + to the solutions containing alkali metals does not result in substantial Ag + complexation. Analysis of a solution containing only transition metal, not alkali metal, cations indicates that 4 forms complexes with Zn + and Ag + along with substantial complexation of Na + from residual sodium present in the solvents.