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Minor Groove (minor + groove)
Terms modified by Minor Groove Selected AbstractsInfluence of , -Alanine on Hairpin Polyamide Orientation in the DNA Minor GrooveHELVETICA CHIMICA ACTA, Issue 6 2003Victor Antiparallel polyamides containing 1H -pyrrole, 1H -imidazole, and 3-hydroxy-1H -pyrrole amino acids display a preference for minor-groove binding oriented NC with respect to the 5,-3, direction of the DNA helix. We find that replacement of a central Py/Py pair with a ,/, pair within a ten-ring hairpin relaxes the orientation preference and, for some DNA sequences, causes the polyamide to prefer the opposite CN orientation. Substitution of the achiral , -aminobutanoic acid (,) with either (R)(or S)-2-(acetylamino)-4-aminobutanoic acid moderates the orientation preference of the 2- , -2-hairpin. [source] XNA, (xylo Nucleic Acid): A Summary and New DerivativesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 11 2005B. Ravindra Babu Abstract Fully modified homopyrimidine 2'-deoxy- xylo nucleic acid (dXNA) form triple helixes with complementary DNA/RNA with thermal stabilities comparable to those of the corresponding DNA:DNA and DNA:RNA duplexes. However, a single or few insertions of dXNA monomers in a DNA strand significantly lower duplex stabilities. The dXNA monomers are known to adopt predominantly an N -type furanose conformation in solution. With a desire to increase the binding affinity, seven sugar-modified XNA monomers (H, F, N, M, K, P and Q) have been synthesised and their effect on hybridization towards DNA and RNA complements studied. The introduction of 2'-fluoro and 2'-hydroxy substituents was expected to induce conformational restriction towards C3'- endo -type furanose conformation of monomer F derived from 1-(2'-deoxy-2'-fluoro-,- D -xylofuranosyl)thymine and monomer H derived from 1-(,- D -xylofuranosyl)thymine. The presence of functionalites facing the minor groove as in 1-(2'-amino-2'-deoxy-2'- N,4'- C -methylene-,- D -xylofuranosyl)thymine (monomer N), 1-[4- C -(N -methylpiperazinyl)methyl-,- D -xylofuranosyl]thymine (monomer P), 1-(4- C -piperazinylmethyl-,- D -xylofuranosyl)thymine (monomer Q), 1-(4- C -hydroxymethyl-,- D -xylofuranosyl)thymine (monomer M) and 9-(4- C -hydroxymethyl-,- D -xylofuranosyl)adenine (monomer K) was studied, with monomer N being locked in an N -type furanose conformation. Besides, an efficient synthesis of known xylo -LNA phosphoramidite 19, required for the incorporation of 1-(2'- O,4'- C -methylene-,- D -xylofuranosyl)thymine (monomer L) is described. For comparison, hydridization data of various XNAs reported in the literature are included in the discussion section. The thermal denaturation studies show that XNAs containing conformationally locked monomers (N and L) display improved binding affinity, and that partially modified DNA/XNA chimera, or fully modified XNA display preferential hybridization towards RNA complements. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Oligodeoxynucleotide Duplexes Containing (5,S)-5,- C -Alkyl-Modified 2,-Deoxynucleosides: Can an Alkyl Zipper across the DNA Minor-Groove Enhance Duplex Stability?HELVETICA CHIMICA ACTA, Issue 11 2003Huldreich Trafelet A series of oligonucleotides containing (5,S)-5,- C -butyl- and (5,S)-5,- C -isopentyl-substituted 2,-deoxyribonucleosides were designed, prepared, and characterized with the intention to explore alkyl-zipper formation between opposing alkyl chains across the minor groove of oligonucleotide duplexes as a means to modulate DNA-duplex stability. From four possible arrangements of the alkyl groups that differ in the density of packing of the alkyl chains across the minor groove, three (duplex types I,III, Fig.,2) could experimentally be realized and their duplex-forming properties analyzed by UV-melting curves, CD spectroscopy, and isothermal titration calorimetry (ITC), as well as by molecular modeling. The results show that all arrangements of alkyl residues within the minor groove of DNA are thermally destabilizing by 1.5,3°/modification in Tm. We found that, within the proposed duplexes with more loosely packed alkyl groups (type- III duplexes), accommodation of alkyl residues without extended distorsion of the helical parameters of B-DNA is possible but does not lead to higher thermodynamic stability. The more densely packed and more unevenly distributed arrangement (type- II duplexes) seems to suffer from ecliptic positioning of opposite alkyl groups, which might account for a systematic negative contribution to stability due to steric interactions. The decreased stability in the type- III duplexes described here may be due either to missing hydrophobic interactions of the alkyl groups (not bulky enough to make close contacts), or to an overcompensation of favorable alkyl-zipper formation presumably by loss of structured H2O in the minor groove. [source] Theoretical study of the interaction between a high-valent manganese porphyrin oxyl-(hydroxo)-Mn(IV)-TMPyP and double-stranded DNAJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 7 2003Philippe Arnaud Abstract Cationic porphyrin derivatives such as meso-tetrakis(4- N -methylpyridinium)porphyrin, TMPyP, have been shown to interact with double-stranded DNA. The manganese derivative, Mn(III)-TMPyP, activated by an oxygen donor like potassium monopersulfate, provides an efficient DNA-cleaving system. Previous experimental work1 has shown that DNA cleavage by the Mn(III)-TMPyP/KHSO5 system was due to an oxidative attack, within the minor groove of B-DNA, at the C5, or C1, carbons of deoxyribose units. The aim of this study was to use molecular modeling to elucidate the specificity of the interactions between the transient active species oxyl-Mn(IV)-TMPyP and the DNA target. Geometric parameters, charges, and force field constants consistent with the AMBER 98 force field were calculated by DFT methods. Molecular modeling (mechanics and dynamic simulations) were performed for oxyl-(hydroxo)-Mn(IV)-TMPyP bound in the minor groove of the dodecamer d(5,-TCGTCAAACCGC)-d(5,-GCGGTTTGACGA). Geometry, interactions, and binding energy of the metalloporphyrin located at the A.T triplet region of the dodecamer were analyzed. These studies show no significant structural change of the DNA structure upon ligand binding. Mobility of the metalloporphyrin in the minor groove was restrained by the formation of a hydrogen bond between the hydroxo ligand trans to the metal-oxyl and a DNA phosphate, restricting the access of the oxyl group to the (pro-S) H atom at C5,. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 797,805, 2003 [source] Binding of proteins to the minor groove of DNA: What are the structural and energetic determinants for kinking a basepair step?JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2003David Bosch Abstract The structural and energetic determinants for kinking a basepair step by minor groove,insertion of the protein side chains of PurR, LacI, LEF,1, IHF, Sac7d, and Sso7d, have been calculated by molecular dynamics/potential of mean force simulations. The structural determinants of the kinked structures are: two contiguous furanose rings achieve different conformations, in the region of C3,endo (A,DNA) and C2,endo (B,DNA); the , torsion angle always takes values characteristic of the C2,endo conformation of B,DNA, independently of sugar puckering; and protein side chain insertion increases slide (from negative to positive values), rise, and roll, and decreases twist. The energetic determinants of DNA kinking are: the conformational transition of the sugar,phosphate backbone is not energetically demanding; the relative importance of the interbase parameters in the free energy penalty is slide, followed by twist and rise, and concluding with shift and roll; and the characteristic increase of roll and decrease of twist, upon side chain insertion, tends to stabilize the process of DNA kinking. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 682,691, 2003 [source] Detection of Texas red-labelled double-stranded DNA by non-enzymatic peroxyoxalate chemiluminescenceLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 3 2001F. Javier Alba Abstract We have found previously that different fluorescent dyes cannot be efficiently excited by the bis(2,4,6-trichlorophenyl)oxalate (TCPO),H2O2 reaction when they are intercalated between the DNA bases or bound to the minor groove of the double helix. Here we show that the fluorescent dye Texas red, covalently bound to the 3, ends of double-stranded DNA molecules, exhibits a high emission intensity when excited by the TCPO,H2O2 reaction. In this case, the charge transfer between the intermediate produced in the peroxyoxalate chemiluminescent reaction and Texas red can take place because this fluorophore is not buried inside the DNA structure. We describe the application of this chemiluminescent reaction to the detection of blotted DNA on nylon membranes. Copyright © 2001 John Wiley & Sons, Ltd. [source] DNA minor groove binders as potential antitumor and antimicrobial agentsMEDICINAL RESEARCH REVIEWS, Issue 4 2004Pier Giovanni Baraldi Abstract DNA minor groove binders constitute an important class of derivatives in anticancer therapy. Some of these compounds form noncovalent complexes with DNA (e.g., distamycin A, Hoechst 33258, and pentamidine) while others DNA-binding compounds (such as CC-1065) cause cleavages in the DNA backbone. In this article, we have reviewed the minor groove binders currently in preclinical evaluation in the last years. Diarylamidines such as DAPI, berenil, and pentamidine; bis-benzimidazoles such as Hoechst 33258; ecteinascidins, pyrrololo [2,1- c]-[1,4]-benzodiazepines (PBDs), CC-1065, and distamycins are the classes discussed in this review article. A special section has been dedicated to hybrid molecules resulted by the combination of two minor groove binders, especially for derivatives of naturally occurring antitumor agents, such as anthramycin or the alkylating unit of the antibiotic CC-1065, and distamycin frames. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 4, 475,528, 2004 [source] Comparative Study of Activities between Verbascoside and Rutin by Docking MethodMOLECULAR INFORMATICS, Issue 1 2003Kun Gao Abstract Verbascoside and rutin possess anti-cancer properties and are capable of repairing DNA damaged by oxygen radicals, acting as powerful antioxidants. Based on kinetic measurements and experiments on tumor cells, docking studies of the two ligand molecules with the receptor telomeric DNA fragments have been carried out. The docking calculations performed using JUMNA software showed that the both molecules can be docked into the minor groove of telomeric DNA and form complexes with suitable geometry for electron transfer between guanine radical and ligands. The reaction mechanism via the electron transfer process is further confirmed through energy calculations for transition states using MOPAC 93 program. Complexes can be formed without major distortion of DNA structure and are further stabilized by the interaction of DNA with the saccharide side-groups. By comparing their energies, the difference of activities of the two compounds can be explained. [source] Coiled-coil conformation of a pentamidine,DNA complexACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2010Tadeo Moreno The coiled-coil structure formed by the complex of the DNA duplex d(ATATATATAT)2 with pentamidine is presented. The duplex was found to have a mixed structure containing Watson,Crick and Hoogsteen base pairs. The drug stabilizes the coiled coil through the formation of cross-links between neighbouring duplexes. The central part of the drug is found in the minor groove as expected, whereas the charged terminal amidine groups protrude and interact with phosphates from neighbouring molecules. The formation of cross-links may be related to the biological effects of pentamidine, which is used as an antiprotozoal agent in trypanosomiasis, leishmaniasis and pneumonias associated with AIDS. The DNA sequence that was used is highly abundant in most eukaryotic genomes. However, very few data are available on DNA sequences which only contain A·T base pairs. [source] Binding of Helix-Threading Peptides to E. coli 16S Ribosomal RNA and Inhibition of the S15,16S ComplexCHEMBIOCHEM, Issue 12 2005Barry D. Gooch Abstract Helix-threading peptides (HTPs) constitute a new class of small molecules that bind selectively to duplex RNA structures adjacent to helix defects and project peptide functionality into the dissimilar duplex grooves. To further explore and develop the capabilities of the HTP design for binding RNA selectively, we identified helix 22 of the prokaryotic ribosomal RNA 16S as a target. This helix is a component of the binding site for the ribosomal protein S15. In addition, the S15,16S RNA interaction is important for the ordered assembly of the bacterial ribosome. Here we present the synthesis and characterization of helix-threading peptides that bind selectively to helix 22 of E. coli 16S RNA. These compounds bind helix 22 by threading intercalation placing the N termini in the minor groove and the C termini in the major groove. Binding is dependent on the presence of a highly conserved purine-rich internal loop in the RNA, whereas removal of the loop minimally affects binding of the classical intercalators ethidium bromide and methidiumpropyl,EDTA,Fe (MPE,Fe). Moreover, binding selectivity translates into selective inhibition of formation of the S15,16S complex. [source] Discrimination of Single-Nucleotide Alterations by G-Specific Fluorescence QuenchingCHEMBIOCHEM, Issue 6 2005Chikara Dohno Dr. Abstract A new strategy for the detection of single-base alterations through fluorescence quenching by guanine (G) is described. We have devised a novel base-discriminating fluorescent (BDF) nucleoside, 4,PyT, that contains a pyrenecarboxamide fluorophore at the thymidine sugar's C4,-position. 4,PyT-containing oligodeoxynucleotides only exhibited enhanced fluorescence in response to the presence of a complementary adenine base. In contrast, the fluorescence of mismatched duplexes containing 4,PyT/N base pairs (N=C, G, or T) was considerably weaker. This highly A-selective fluorescence was a product of guanine-specific quenching efficiency; when the complementary base to 4,PyT was a mismatch, the pyrenecarboxamide fluorophore was able to interact intimately with neighboring G bases (the most likely interaction in the case of intercalation), so effective quenching by the G bases occurred in the mismatched duplexes. In contrast, duplexes containing 4,PyT/A base pairs exhibited strong emission, since in this case the fluorophores were positioned in the minor groove and able to escape fluorescence quenching by the G bases. [source] Structures and Stabilities of Small DNA Dumbbells with Watson,Crick and Hoogsteen Base PairsCHEMBIOCHEM, Issue 7 2003Nuria Escaja Dr. Abstract The structures and stabilities of cyclic DNA octamers of different sequences have been studied by NMR and CD spectroscopy and by restrained molecular dynamics. At low oligonucleotide concentrations, some of these molecules form stable monomeric structures consisting of a short stem of two base pairs connected by two mini-loops of two residues. To our knowledge, these dumbbell-like structures are the smallest observed to date. The relative stabilities of these cyclic dumbbells have been established by studying their melting transitions. Dumbbells made up purely of GC stems are more stable than those consisting purely of AT base pairs. The order of the base pairs closing the loops also has an important effect on the stabilities of these structures. The NMR data indicate that there are significant differences between the solution structures of dumbbells with G,C base pairs in the stem compared to those with A,T base pairs. In the case of dumbbells with G,C base pairs, the residues in the stem form a short segment of a BDNA helix stabilized by two Watson,Crick base pairs. In contrast, in the case of d,pCATTCATT,, the stem is formed by two A,T base pairs with the glycosidic angles of the adenine bases in a syn conformation, most probably forming Hoogsteen base pairs. Although the conformations of the loop residues are not very well defined, the thymine residues at the first position of the loop are observed to fold back into the minor groove of the stem. [source] Conformational Transition in the Aminoacyl t-RNA Site of the Bacterial Ribosome both in the Presence and Absence of an Aminoglycoside AntibioticCHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2007Samy O. Meroueh Peptide bonds are made at the ribosomal decoding site. Structural information reveals that two bases in the RNA that constitute the decoding site, A1492 and A1493, can have both intrahelical and extrahelical conformations. Aminoglycoside antibiotics bind to the decoding site, and the structural information reveals the two bases in the extrahelical positions. We have shown by explicit-solvent molecular dynamics simulations and free-energy calculations that ribosomal RNA bases A1492 and A1493 are inherently prone to sampling conformational states that include both intrahelical and extrahelical positions. The simulations reveal that base flipping occurs through the minor groove of the double helix. Furthermore, free-energy calculations for the conformational change of the bases to the extrahelical positions in both processes are exergonic and highly favorable. It is likely that the correct codon-anticodon recognition by mRNA and tRNA arrests the bases in extrahelical conformations in the course of normal translation. In contrast, the sequestration of the aminoglycoside antibiotic at the decoding site facilitates the conformational change of the bases to the extrahelical position. Once the antibiotic is bound, the extrahelical positions for the bases are highly favored based on contributions by both electrostatic and entropic components of the free energy for the process. [source] Sugar,Oligoamides: Bound-State Conformation and DNA Minor-Groove-Binding Description by TR-NOESY and Differential-Frequency Saturation-Transfer-Difference ExperimentsCHEMISTRY - A EUROPEAN JOURNAL, Issue 8 2008Florence Souard Abstract Selective-frequency saturation-transfer-difference (STD) spectra allow the description of complexes established between minor-groove binders and long tracts of calf thymus DNA (ct-DNA). Two sets of experiments with selective saturation of either the H1, or H4,/H5,/H5,, proton NMR regions of deoxyribose allow the description of the ligand residues close to the inner (H1,) and outer regions (H4,/H5,/H5,,) of the minor groove of double-helical DNA. A series of complexes of sugar,oligoamides (2,6) with ct-DNA have been studied by both TR-NOESY and STD experiments. The binding mode of the complexes is similar to that of netropsin (1) and allows us to define a general binding mode for this family of ligands, in which an NH rim points towards the internal area (inner region) and a CH3 rim points towards the external part (outer region) of the minor groove of DNA. Also by means of both TR-NOESY and STD experiments, a description of the asymmetric centers of the sugar residue close to the inner and outer regions of the groove has been achieved. These results confirm that the sugar is responsible for the differences previously found in binding energetics. 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