Crystal Structure of Chiral γPNA with Complementary DNA Strand: Insights into the Stability and Specificity of Recognition and Conformational Preorganization.

We have determined the structure of a PNA-DNA duplex to 1.7 A resolution by multiple- wavelength anomalous diffraction phasing method on a zinc derivative. This structure represents the first high-resolution 3D view of a hybrid duplex containing a contiguous chiral PNA strand with complete γ-backbon...

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Publicado en:Journal of the American Chemical Society Vol. 132; no. 31; pp. 10717 - 10728
Autores principales: Yeh, Joanne I., Shivachev, Boris, Rapireddy, Srinivas, Crawford, Matthew J., GiI, Roberto R., Du, Shoucheng, Madrid, Marcela, Ly, Danith H.
Formato: Artículo
Publicado: American Chemical Society 8/11/2010
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: 8/11/2010
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      pub: American Chemical Society
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        10.1021/ja907225d
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        atl: Crystal Structure of Chiral γPNA with Complementary DNA Strand: Insights into the Stability and Specificity of Recognition and Conformational Preorganization.
      aug:
        au:
          Yeh, Joanne I.
          Shivachev, Boris
          Rapireddy, Srinivas
          Crawford, Matthew J.
          GiI, Roberto R.
          Du, Shoucheng
          Madrid, Marcela
          Ly, Danith H.
        affil:
          Department of Structural Biology, University of Pittsburgh Medical School 1036 BST3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15260, USA
          Department of Chemistry and Center for Nucleic Acids Science and Technology (CNAST), Mellon Institute, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA
          Pittsburgh Supercomputing Center, Pittsburgh, Pennsylvania 15213, USA
      su:
        Chirality
        Antisense DNA
        Crystals
        Stability (Mechanics)
        Peptides
        Wavelengths
        Optical diffraction
        Nucleic acid hybridization
      sug:
        subj:
          Chirality
          Antisense DNA
          Crystals
          Stability (Mechanics)
          Peptides
          Wavelengths
          Optical diffraction
          Nucleic acid hybridization
      ab: We have determined the structure of a PNA-DNA duplex to 1.7 A resolution by multiple- wavelength anomalous diffraction phasing method on a zinc derivative. This structure represents the first high-resolution 3D view of a hybrid duplex containing a contiguous chiral PNA strand with complete γ-backbone modification (`yPNA"). Unlike the achiral counterpart, which adopts a random-fold, this particular yPNA is already preorganized into a right-handed helix as a single strand. The new structure illustrates the unique characteristics of this modified PNA, possessing conformational flexibility while maintaining sufficient structural integrity to ultimately adopt the preferred P-helical conformation upon hybridization with DNA. The unusual structural adaptability found in the γPNA strand is crucial for enabling the accommodation of backbone modifications while constraining conformational states. In conjunction with NMR analysis characterizing the structures and substructures of the individual building blocks, these results provide unprecedented insights into how this new class of chiral γPNA is preorganized and stabilized, before and after hybridization with a cDNA strand. Such knowledge is crucial for the future design and development of PNA for applications in biology, biotechnology, and medicine.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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          year: 2010
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