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Alice M. Delvolve
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Speaker: Alice M. Delvolve, National Institute on Drug Abuse (NIDA), NIH, Baltimore, MD 21224
Topic: Modeling of PNA-DNA Non-Covalent Complexes
Place: Building 549, Conference Room A, NCI at Frederick, Frederick, MD
Time: Tuesday, March 11, 2008, at 2:00 PM
Abstract: Specific inter molecular recognition is at the heart of many biological processes (reading and expression of genetic information, immune defense, cellular signal transmission, etc). It results into molecular associations, via "weak" noncovalent interactions, leading to structural changes which modify their biological function. Understanding such systems has at least two advantages: resolving the biochemical mechanisms that govern DNA's chemical properties and applying the acquired knowledge for medical goals. As an example, the understanding of the binding of DNA single strands by specific recognition of their nucleobases was at the origin of the discovery of A-T and G-C pairing and therapeutic agents that can block this interaction have been utilized in cancer and viral diseases to prevent cellular proliferation.
In the present work, the synthetic molecule is a peptide nucleic acid (PNA) developed by Ole Buchardt and the Peter E. Nielsen. In this work we analyzed these polymers and their interactions using ESI instruments coupled to an ion trap or to a Fourier Transform Ion Cyclotron Resonance. PNA single strands were studied in both positive and negative mode in order to elucidate their behavior in PNAa/DNAb noncovalent associations. Then, the behavior of such multiplexes was investigated in the gas phase as a function of their charge state. From the observation of their dissociation orientation, a model has been proposed to explain the stability of these noncovalent complexes. In addition, the stability of PNA/DNA/PNA specific associations in the gas phase was compared to their stability in solution and found to be very similar.
The slides to this seminar are in a 1.8 Megabyte PDF file (as well as supplemental material), which can be opened and read by using the free Adobe Acrobat Reader®.
Accompanying Poster: "The Molecular Structure of the Interface of the DA Receptor Containing Heteromers", authored by Shelley N. Jackson and Amina S. Woods, National Institute on Drug Abuse (NIDA), NIH, Baltimore, MD 21224
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Updated 11-March-2008
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