Biomedical subjects
Publications and source records attributed to Yamuna Krishnan-Ghosh.
The tetramolecular PNA quadruplex motif has been probed using a dynamic covalent chemistry (DCC) approach to create and characterize a bimolecular PNA quadruplex.
A tetranucleotide sequence d(GGGT) has been shown to self-assemble into an interlocking quadruplex dimer. UV-melting studies indicated the existence of two species that each showed distinct quadruplex melting transitions, a low-T(m) species, Q(l), and a high-T(m) species, Q(h). Conditions were controlled to favor the formation of either Q(l) or Q(h). Q(l) and Q(h) each showed circular dichroism spectra characteristic of parallel quadruplexes. Negative ion nano-electrospray ionization mass spectrometry confirmed that Q(l) was a tetrameric complex, d(GGGT)(4), and Q(h) was an octameric complex, d(GGGT)(8). High-resolution (1)H NMR spectroscopy evidenced that d(GGGT)(4) was a C(4)-symmetric parallel tetramolecular quadruplex. The (1)H NMR spectrum of d(GGGT)(8) was consistent with a structure formed by the dimerization of a parallel, "slipped" tetramolecular quadruplex that has its diagonal strands staggered by one base. This "slippage" results in two guanine bases at the 5' end of the quadruplex being presented diagonally that are not involved in tetrads. Two such "slipped" quadruplexes dimerize via these free G-bases at the 5' ends by forming an extra G-tetrad. Each "slipped" quadruplex contributes two guanine bases to this extra G-tetrad. The formation of a novel GTGT tetrad is also observed at both the 3' ends of the interlocked quadruplex dimer.
A tetrameric PNA, TGGG, has been shown to form an intermolecular G-quadruplex. Nanoelectrospray mass spectrometry, combined with solution-phase H/D exchange, established formation of a specific tetramolecular complex. UV melting studies show that this complex undergoes a quadruplex melting transition. This is a novel four-stranded structure that offers the gross structural features of a DNA quadruplex, but without the negatively charged backbone.
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An expedient synthesis of the polymer-supported aldehyde 3, as a Garner aldehyde equivalent, is described. Oxazolidine 3 may be obtained through preformation of aldehyde linker 4 in solution and loaded onto amine-terminating resin under peptide-coupling conditions, or alternatively via oxidation of polymer-bound alcohol 14. The integrity of the serine-derived stereocenter is maintained through all steps of the synthesis.
Metal chelating iminodiacetic acid moieties were appended to abutting ends of two 9-mer oligonucleotides designed to hybridize contiguously on an 18-mer target. Chelation of 1 equivalent of Gd3+ cooperatively increases affinities of the oligonucleotides to the single stranded DNA target as evidenced by a 15 degrees C increase in Tm of the complex.