International Review of Biophysical Chemistry最新文献

{"title":"G-Quadruplex Superstructure in the hTERT Core Promoter: Stabilization by Monomer Self-Stacking","authors":"Emanuela Micheli, Matteo Martufi, A. Galati, M. Franceschin, P. Santis, M. Savino, S. Cacchione","doi":"10.15866/IREBIC.V2I4.1528","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I4.1528","url":null,"abstract":"G-quadruplex-forming are widespread in eukaryotic genomes. In particular, G-quadruplex motifs have been found in the promoter region of 40% human genes. One of these genes is hTERT, encoding the catalytic subunit of human telomerase, whose up-regulated expression is responsible for the unlimited proliferative potential of most cancer cells. hTERT core promoter exhibits a high potential for G-quadruplex formation, containing nine partially overlapping PQS (putative quadruplex sequence) in a G-rich region of 68 nucleotides. Here we show the formation of a superstructure in the hTERT promoter deriving from the simultaneous folding of three adjacent G-quadruplex structures. Interestingly, G-quadruplex ligands are able to stabilize hTERT G-quadruplex structures and to alter transcription from the hTERT promoter, suggesting that the formation of a G-quadruplex superstructure could play a role in regulating gene transcription","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"81 1","pages":"153-155"},"PeriodicalIF":0.0,"publicationDate":"2011-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76782701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectroscopic Studies on Binding of Porphyrin-Phenazine Conjugate to Intramolecular G-Quadruplex Formed by 22-mer Oligonucleotide","authors":"V. Zozulya, O. Ryazanova, I. Voloshin, L. Dubey, I. Dubey","doi":"10.15866/IREBIC.V2I4.1522","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I4.1522","url":null,"abstract":"The interaction of the novel cationic porphyrin – imidazophenazine conjugate (TMP3-Pzn), as well as its zinc (II) and manganese (III) metallocomplexes  with intramolecular G-quadruplex formed by 22-mer oligodeoxynucleotide d[AGGG(TTAGGG)3] of human telomeric repeat (22G4) was studied.  Techniques of absorption and polarized fluorescent spectroscopy as well as absorption melting at 295 nm were used. The binding affinity of the conjugates to the quadruplex was studied using titration experiments registering the dependence of the fluorescence intensity and polarization degree for porphyrin moieties  on quadruplex/ligand molar ratio (P/D). All investigations were carried out in 2 mM phosphate buffer (pH6.9) containing 0.5 mM EDTA and 0.1 M NaCl. Spectroscopic characteristics of the TMP3-Pzn and ZnTMP3-Pzn conjugates evidence the formation of internal heterodimers with stacking between porphyrin and phenazine chromophores, although in the case of MnTMP3-Pzn it has not occurred. It was established that all the conjugates reveal high binding affinities to the intra-molecular G-quadruplex, probably, via external groove binding of porphyrin moiety. The complex formation is accompanied by the increase in the fluorescence intensity and polarization degree of porphyrin fragments. It should be noted that negligibly small fluorescence of manganese porphyrin moiety flames up by near 20 times under the binding, being the novel observation for manganese complex. It was found that ZnTMP3-Pzn and MnTMP3-Pzn stabilize the G-quadruplex structure increasing the transition midpoint temperature by 3 °C, whereas non-metallated TMP3-Pzn conjugate decreases it by approximately 2 °C. Despite of the opposite changes in G-quadruplex melting temperature, a simultaneous increase in the transition enthalpy and entropy was determined for all conjugates, which gives a some stabilizing increment in the Gibbs standard free energy. In the case of metal complexes, 10-fold increase in the 22G4 folding equilibrium constant at 37 °C was determined","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"40 1","pages":"112-119"},"PeriodicalIF":0.0,"publicationDate":"2011-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84849809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Protein Binding on DNA G-Quadruplex Structures","authors":"Luca Ginnari-Satriani, V. Casagrande, A. Alvino, Alessandro Altieri, Pierre Murat, E. Defrancq, C. Lombardo, S. Neidle, A. Bianco, G. Ortaggi, M. Franceschin","doi":"10.15866/IREBIC.V2I4.1525","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I4.1525","url":null,"abstract":"We report here a study of the binding affinity of a triazatruxene based G-quadruplex ligand and three derivatives to G-quadruplex structures and their selectivity with respect to duplex DNA. The parent compound AZATRUX is the best compound of the series, both in terms of affinity and selectivity","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"16 1","pages":"135-141"},"PeriodicalIF":0.0,"publicationDate":"2011-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74590609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Development of c-myc G-Quadruplex Ligands","authors":"V. P. Ma, Ka-Ho Leung, D. Chan, W. Lam, C. Leung, Dik‐Lung Ma","doi":"10.15866/IREBIC.V2I4.1523","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I4.1523","url":null,"abstract":"In this review, we summarize recent findings in the development of c-myc G-quadruplex ligands. Several features such as expanded aromatic rings, flexible molecules, dinuclear metal complexes, oligomers and G-quartet based ligands have been demonstrated to be advantageous for providing higher selectivity towards the c-myc G-quadruplex over duplex structures. High throughput screening methods including competition dialysis, G4 FID, FRET-based melting assay, direct ELISA and in silico virtual screening for analyzing the interaction between the ligands and the c-myc G-quadruplex are discussed. In particular, in silico virtual screening has been demonstrated to be a valuable means for the discovery of selective G-quadruplex ligands. Using this approach, ligands selective for the c-myc G-quadruplex have been successfully identified","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"55 1","pages":"120-128"},"PeriodicalIF":0.0,"publicationDate":"2011-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76007042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pressure Effects on G-Quadruplex Structures Stabilized by Two Different Counter-Ions","authors":"E. J. Baldassarri, M. G. Ortore, C. Ferrero, S. Finet, F. Spinozzi, P. Mariani","doi":"10.15866/IREBIC.V2I4.1526","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I4.1526","url":null,"abstract":"It is well known that the formation of G-quadruplex by guanosine derivatives strongly depends on counter-ions. To investigate quadruplex stability in the presence of different counter-ions and in the absence of a covalent axial backbone, high-pressure X-ray diffraction experiments have been performed on lyotropic phases of guanosine 5’-monophosphate (GMP) in the form of sodium and ammonium salts. As a result, concentration-pressure phase diagrams were obtained in a pressure range from 1 bar to about 2 kbar, and the structural properties of the different phases derived. Interestingly, cholesteric (Ch) and hexagonal (H) columnar phases were found in both GMP salts, but during compression a reverse behavior was detected: in GMP sodium salt, pressure induces a H-Ch phase transition, while in GMP ammonium salt the induced transition is Ch-H. Different counter-ion stabilization, which control quadruplex length and the consequence of lateral interactions, probably explain such observation","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"67 4","pages":"142-146"},"PeriodicalIF":0.0,"publicationDate":"2011-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91441459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Structure and Antiproliferative Activity of Cationic Porphyrin - Imidazophenazine Conjugate","authors":"L. Dubey, Mykola M. Ilchenko, V. Zozulya, O. Ryazanova, P. Pogrebnoy, I. Dubey","doi":"10.15866/IREBIC.V2I4.1527","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I4.1527","url":null,"abstract":"New conjugate of G-quadruplex ligand, cationic tris(methylpyridinium)porphyrin, and its Zn(II) and Mn(III) metal complexes with a neutral intercalating agent imidazophenazine were synthesized. The synthesis was based on the coupling of carboxyalkyl derivative of the porphyrin with N1-aminoalkylated dye. Spectral-fluorescent studies and density functional quantum-chemical calculations suggest the formation of intramolecular complexes between the two chromophores for non-metalated hybrid and zinc(II) derivative. The conjugates have been found to inhibit the growth of tumor cells of mouse Lewis lung carcinoma in vitro at micromolar concentrations. Metal complexes were several times more active than the non-metalated hybrid. The most efficient Zn(II) complex suppressed the tumor cells with IC50 5.9 M","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"79 1","pages":"147-152"},"PeriodicalIF":0.0,"publicationDate":"2011-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86891183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Density Functional Study of the Structure of Guanine Octets in Aqueous Medium","authors":"Mykola M. Ilchenko, I. Dubey","doi":"10.15866/IREBIC.V2I3.1516","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I3.1516","url":null,"abstract":"The structures and energies of guanine quartets and octets in water were determined by DFT (Density Functional Theory) calculations using M06-2X functional and 6-31G(d, p) basic set. Guanine quartets in vacuum were found to have not only the Hoogsteen or bifurcated, but also mixed system of hydrogen bonds; in water the latter two forms are transformed into the classic Hoogsteen-type structure. Four stable configurations of G-octets with D4, C4 and S4 symmetry formed by the pairs of guanine quartets with Hoogsteen, bifurcated or mixed system of H-bonds were identified. The most advantageous structure of the G-octet molecular system in aqueous medium was shown to be S4-symmetric structure consisting of the pair of mixed Hoogsteen-bifurcated type G-quartets","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"78 1","pages":"82-86"},"PeriodicalIF":0.0,"publicationDate":"2011-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73852451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Switching between Supramolecular Assemblies of Lipophilic Guanosine Derivatives Triggered by External Stimuli","authors":"S. Masiero, Lucia Gramigna, P. Neviani, R. Perone, S. Pieraccini, G. Spada","doi":"10.15866/IREBIC.V2I3.1518","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I3.1518","url":null,"abstract":"Depending on the experimental conditions, lipophilic guanosines (LipoGs) can undergo different self-assembly pathways based on different H-bonded motifs, e.g. the cyclic discrete G-quartet and the “infinite” tape-like G-ribbon. The switching between different supramolecular motifs have been obtained by a variety of external stimuli. After a general presentation of the LipoG self-assembly, in this mini-review we will discuss, the case of three different stimuli. A first example is represented by chemical stimuli: addition of an alkali metal ion stabilizes the G-quartet while its removal shifts the equilibrium toward the G-ribbon. In the second case, a lipoG armed with a terthiophene unit undergoes a pronounced variation of its supramolecular organisation by changing the polarity of the solvent: in chloroform the derivative assembles via H-bonding in a guanosine driven structure, while in the more polar (and H-bond competing) acetonitrile different aggregates are observed, where the terthiophene chains are - stacked in a helicoidal arrangement. Finally, a third type of stimulus is represented by light: the photocontrolled self-assembly of a modified guanosine nucleobase with a photoactive unit at C8 is obtained selecting the appropriate wavelength","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"22 1","pages":"87-95"},"PeriodicalIF":0.0,"publicationDate":"2011-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83741414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do Anions Exert any Structural Changes on Dimeric d(G4T4G4)2 Quadruplex in Aqueous Solution","authors":"P. Šket, Rok Pirh, J. Plavec","doi":"10.15866/IREBIC.V2I3.1513","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I3.1513","url":null,"abstract":"It is well known that the presence of cations is necessary for G-quartet formation due to their role in reducing repulsions amongst guanine carbonyl oxygen atoms and additionally enhancing base-base stacking interactions. However, not much is known about the influence of anions on G-quadruplex formation by G-rich oligonucleotides in aqueous solution. In the presence of sodium halides, acetate, nitrate and BPh4- folding was almost complete, while only partial folding has been observed with NaBF4 and NaPF6. Detailed evaluation of 1H NMR spectra of d(G4T4G4)2 in the presence of nine different sodium salts indicates minor differences in loop regions as well as in structure of G-quadruplex core. Comparison of inter-proton distances obtained from NOESY spectra showed slightly different orientations of thymine residues in loop regions and changes in stacking interactions between G-quartets, which are most pronounced in the case of G-quadruplex folded in the presence of NaPF6","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"66 1","pages":"68-73"},"PeriodicalIF":0.0,"publicationDate":"2011-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80187254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Template Assembled Synthetic G-Quadruplex: a Novel Biomolecular System for Investigating the Interactions of Ligands with Constrained Quadruplex Conformation","authors":"Romaric Bonnet, Pierre Murat, N. Spinelli, A. V. D. Heyden, P. Labbé, P. Dumy, E. Defrancq","doi":"10.15866/IREBIC.V2I3.1515","DOIUrl":"https://doi.org/10.15866/IREBIC.V2I3.1515","url":null,"abstract":"We report on the design of a new biomolecular device based on the concept of Template Assembled Synthetic G-Quadruplex (TASQ), where quadruplex DNA structures are assembled on a scaffold for constraining G-quadruplex conformation. As a proof of concept, parallel-stranded conformation of G-quadruplex was prepared by using a cyclodecapeptide as the template. As anticipated the use of the scaffold allows the precise control of the conformation of the quadruplex and increases dramatically the stability of the motif. This device was used for investigating by Surface Plasmon Resonance the affinity of ligands for G-quadruplex DNA","PeriodicalId":14377,"journal":{"name":"International Review of Biophysical Chemistry","volume":"77 1","pages":"78-81"},"PeriodicalIF":0.0,"publicationDate":"2011-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89916788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}