As part of an ongoing effort to explore the effect of major groove electrostatics on the thermodynamic stability and structure of DNA, a 7-deaza-2'-deoxyadenosine:dT (7-deaza-dA:dT) base pair in the Dickerson-Drew dodecamer (DDD) was studied. The removal of the electronegative N7 atom on dA and the replacement with an electropositive C-H in the major groove was expected to have a significant ef...

SJG-136, a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer, is a highly efficient interstrand crosslinking agent that reacts with guanine bases in a 5'-GATC-3' sequence in the DNA minor groove. SJG-136 crosslinks form rapidly and persist compared to those produced by conventional crosslinking agents such as nitrogen mustard, melphalan or cisplatin which bind in the DNA major groove. A panel of Ch...

Drug-like molecules that bind RNA with sequence selectivity would provide valuable tools to elucidate gene expression pathways and new avenues to the treatment of degenerative and chronic conditions. Efforts at discovering such agents have been hampered, until recently, by the limited knowledge of RNA recognition principles. Several recent structures of aminoglycoside-RNA complexes have begun t...

Recently it has been found that stable and accurate molecular dynamics (MD) of B-DNA duplexes can be obtained in relatively inexpensive computational conditions with the bulk solvent represented implicitly, but the minor groove filled with explicit water (J. Am. Chem. Soc. 1998, 120, 10928). The present paper further explores these simulation conditions in order to understand the main factors r...

Hepatitis B virus (HBV) replication is initiated by HBV RT binding to the highly conserved encapsidation signal, epsilon, at the 5' end of the RNA pregenome. Epsilon contains an apical stem-loop, whose residues are either totally conserved or show rare non-disruptive mutations. Here we present the structure of the apical stem-loop based on NOE, RDC and (1)H chemical shift NMR data. The (1)H che...

The potent mutagen/carcinogen 7R,8S-dihydroxy-9S, 10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-B[a]PDE], which is the activated form of benzo[a]pyrene (B[a]P), is able to induce different kinds of mutations (G-->T, G-->A, etc.). One hypothesis for this is that different mutations are induced depending upon the conformation of its major adduct ([+ta]-B[a]P-N2-dG) when bypassed during DN...

Nucleoid associated proteins (NAPs) play a key role in the compaction and expression of the prokaryotic genome. Here we report the organisation of a major NAP, the protein H-NS on a double stranded DNA fragment. For this purpose we have carried out a small angle neutron scattering study in conjunction with contrast variation to obtain the contributions to the scattering (structure factors) from...

Background and objectives: Coumarins have potential anticancer effects. Ferulago macrocarpa (Fenzl) Boiss, is a perennial herb which has shown to have several dihydropyranocoumarins like grandivittin (GRA) and dihydrofuranocoumarins such as prantschimgin (PRA). Previously the antibacterial, cytotoxic and antioxidant effect of GRA and PRA have been reported. Understandi...