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Interactions Between Spermine-Derivatized Tentacle Porphyrins and The Human Telomeric DNA G-Quadruplex.
Sabharwal, Navin C; Chen, Jessica; Lee, Joo Hyun June; Gangemi, Chiara M A; D'Urso, Alessandro; Yatsunyk, Liliya A.
Afiliação
  • Sabharwal NC; Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA. navin.sabharwal.424@gmail.com.
  • Chen J; Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. navin.sabharwal.424@gmail.com.
  • Lee JHJ; Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA. ymchen.017@gmail.com.
  • Gangemi CMA; School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ymchen.017@gmail.com.
  • D'Urso A; Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA. jlee2143@gmail.com.
  • Yatsunyk LA; College of Dentistry, New York University, New York, NY 10010, USA. jlee2143@gmail.com.
Int J Mol Sci ; 19(11)2018 Nov 21.
Article em En | MEDLINE | ID: mdl-30469358
G-rich DNA sequences have the potential to fold into non-canonical G-Quadruplex (GQ) structures implicated in aging and human diseases, notably cancers. Because stabilization of GQs at telomeres and oncogene promoters may prevent cancer, there is an interest in developing small molecules that selectively target GQs. Herein, we investigate the interactions of meso-tetrakis-(4-carboxysperminephenyl)porphyrin (TCPPSpm4) and its Zn(II) derivative (ZnTCPPSpm4) with human telomeric DNA (Tel22) via UV-Vis, circular dichroism (CD), and fluorescence spectroscopies, resonance light scattering (RLS), and fluorescence resonance energy transfer (FRET) assays. UV-Vis titrations reveal binding constants of 4.7 × 106 and 1.4 × 107 M-1 and binding stoichiometry of 2⁻4:1 and 10⁻12:1 for TCPPSpm4 and ZnTCPPSpm4, respectively. High stoichiometry is supported by the Job plot data, CD titrations, and RLS data. FRET melting indicates that TCPPSpm4 stabilizes Tel22 by 36 ± 2 °C at 7.5 eq., and that ZnTCPPSpm4 stabilizes Tel22 by 33 ± 2 °C at ~20 eq.; at least 8 eq. of ZnTCPPSpm4 are required to achieve significant stabilization of Tel22, in agreement with its high binding stoichiometry. FRET competition studies show that both porphyrins are mildly selective for human telomeric GQ vs duplex DNA. Spectroscopic studies, combined, point to end-stacking and porphyrin self-association as major binding modes. This work advances our understanding of ligand interactions with GQ DNA.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Porfirinas / DNA / Telômero / Quadruplex G / Substâncias Intercalantes Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Porfirinas / DNA / Telômero / Quadruplex G / Substâncias Intercalantes Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2018 Tipo de documento: Article