Search PubMed⌕ Search

Biomedical subjects

S Neidle

Publications and source records attributed to S Neidle.

177 records · Page 10Linked to original sources
PubMed1979

Netropsin, a DNA-binding oligopeptide structural and binding studies.

The crystal structure of netropsin, an oligopeptide which binds to DNA, has been determined. The molecule is bowed with the amide groups on the concave side, and the carbonyl and methyl groups on the convex side. The amide groups participate in extensive hydrogen bonding with water molecules; the charged amino end groups interact with the sulfate anions. Binding of netropsin to poly(dA) . poly(dT) under conditions of different ionic strength was also studied. Utilizing the crystallographic as well as the binding data, it is possible to build a model which explains the specificity of this antibiotic.

Circular Dichroism↗
PubMed1978

Drug-nucleic acid interactions: conformational flexibility at the intercalation site.

The conformational features of the intercalation site in polynucleotides were examined. We found that, for all the crystal structures of drug-dinucleoside complexes studied thus far, two torsion angles differ from those found in A RNA (phi and chi) and that alternate sugar puckering is not a prerequisite for intercalation. This intercalation geometry, which is the basis of helix axis displacement in a polymer, would necessitate conformational changes in the adjacent nucleotides. The base-turn angle is less sensitive to the conformation of the backbone than it is to small alterations in the base-pairing geometry. We postulate that this angle is dependent on the nature of the intercalating drug.

Models, Chemical↗
PubMed1978

A 1:2 crystalline complex of ApA:proflavine: a model for binding to single-stranded regions in RNA.

The structure of a 1"2 complex of adenylyl-(3',5')-adenosine phosphate and proflavine hemisulfate has been determined using the methods of x-ray crystallography. Since the ApA does not form a mini double helix, it may serve as a model for the interaction of planar molecules with single stranded nucleic acids. The dinucleotide adopts an extended conformation with the adenines in adjacent molecules forming base pairs. A most unusual feature of the molecule is that it does not obey the "rigid nucleotide" concept although none of the torsion angles occur in energetically unfavourable regions. This is most probably due to the strong interactions between the proflavine and the oligonucleotide.

Acridines↗
PubMed1977

Nucleic acid binding drugs. Part IV. The crystal structure of the anti-cancer agent daunomycin.

The crystal structure has been determined of the anti-cancer drug daunomycin, as the hydrochloride monohydrate pyridine salt. The overall structure, previously determined by X-ray analysis of an N-bromoacetyl derivative (Anguili, R., Foresti, E., Riva Di Sanserverino, L., Isaacs, N.W., Kennard, O., Motherwell, W.D.S., Wampler, D.L. and Arcamone, F. (1971) Nat. New Biol. 234, 78-80) has been confirmed, although substantial conformational differences are observed. The conformation described here is very similar to that found for the related drug carminomycin I (Wani, M.C., Taylor, H.L., Wall, M.E., McPhaill, A.T. and Onan, K.D. (1975) J. Am. Chem. Soc. 97, 5955-5956; Pettit, G.R., Einck, J.J., Herald, C.L., Ode, R.H. Von Dreele, R.B., Brown, P., Brazhnikova, M.G. and Gause, G.F. (1975) J. Am. Chem. Soc. 97, 7387-7388); it is suggested that this represents a significantly stable molecular conformation; an intramolecular C(7)...O(9) hydrogen bond is invoked to account for this. This conformation is likely to be at least close to that of daunomycin when bound to DNA.

Computers↗
PubMed1977

Structure of a dinucleoside phosphate--drug complex as model for nucleic acid--drug interaction.

The crystal structure of a 3:2 complex of the frameshift mutagen proflavine with the dinucleoside phosphate cytidylyl-3'5'-guanosine has been determined. The complex has one drug molecule intercalated between Watson--Crick base pairs of the nucleotide duplex. The other two proflavine molecules are bound to the exterior of the miniature double helix. The orientation of the base pairs in this miniature double helix has aspects similar to that found in RNA 11.

Acridines↗
PubMed1976

The structure of Miracil D, a DNA-binding drug.

The crystal structure of the drug Miracil D has been determined. Although the accuracy of the analysis is limited by disorder, it is apparent that the thioxanthone ring system is planar. The proximal nitrogen atom of the side-chain probably forms an intramolecular hydrogen bond with the carbonyl oxygen. The rest of the side-chain has a large degree of conformational mobility.

Chemical Phenomena↗
PubMed1976

The crystal and molecular structure of an osmium bispyridine adduct of thymine.

The bispyridine osmium adduct of thymine has been crystallised and subjected to an X-ray diffraction analysis. It crystallises in the triclinic space group P1, with cell dimensions a equals 7.975(3), b equals 10.381(3), c equals 11.036(3) A, alpha equals 82.73(2)degrees, beta equals 77.22(3) degrees, gamma equals 101.75(3), and with two molecules in the unit cell. The analysis has shown that the osmium reagent has added cis across the 5,6 thymine bond.

Binding Sites↗
PubMedDate not supplied

G-quadruplexes as therapeutic targets.

The ends of chromosomes (telomeres) consist of tandem repeats of guanine-rich sequences. In eukaryotics, telomeric DNA is single stranded for the final few hundred bases. These single-stranded sequences can fold into a variety of four-stranded structures (quadruplexes) held together by quartets of hydrogen-bonded guanine bases. The reverse transcriptase enzyme telomerase is responsible for maintaining telomeric DNA length in over 85% of cancer cells by catalyzing the synthesis of further telomeric repeats. Its substrate is the single-stranded 3'-telomeric end. Inhibition of telomere maintenance can be achieved by stabilization of a quadruplex structure for the telomere end. A variety of small molecules have been devised to achieve this, ranging from anthraquinones to porphyrins, acridines, and complex polycyclic systems. Structural and mechanistic aspects of these quadruplex complexes are reviewed here, together with a discussion of the issues of selectivity/potency for quadruplex DNAs vs duplex DNA.

Animals↗