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SUMMARY:Fluorescent Nucleoside Analogues with New Properties for Biophysic
 s - Byron W Purse San Diego State University
DTSTART:20191106T160000Z
DTEND:20191106T170000Z
UID:TALK134293@talks.cam.ac.uk
CONTACT:Jo Lockhart
DESCRIPTION:Biophysical probes for the study of nucleic acids are essentia
 l tools in the endeavor to understand the regulation and expression of the
  genetic code. While many capable fluorescent nucleoside analogues exist f
 or these applications\, it has been especially challenging to design analo
 gues that maintain Watson–Crick hydrogen bonding\, offer fluorescence br
 ightness similar to conventional probes\, and that absorb and emit at long
  wavelengths. Moreover\, it is not yet possible to predict how the fluores
 cence of nucleobase analogues will respond to base pairing and stacking. T
 owards our goal of developing nucleoside analogues with new and enhanced f
 luorescent properties and plugging knowledge gaps in the relationship betw
 een base analogue structure and photophysics\, we have designed a series o
 f cytidine analogues with a range of structural modifications and studied 
 their fluorescent responses to base pairing and stacking and the efficienc
 y of their incorporation by DNA and RNA polymerases. This series of cytidi
 ne analogues shows clear relationships between analogue electronic propert
 ies\, the electronics of neighboring bases\, and the fluorescent responses
  to base pairing and stacking\, including with mismatches. One of the anal
 ogues\, DEA-tC\, offers a powerful\, sequence-specific fluorescence turn-o
 n response to base pairing and stacking that is further enhanced in DNA/RN
 A heteroduplexes. The combination of photophysical studies\, NMR structure
  determination of representative duplexes\, and computational work helps t
 o explain the observed photophysical properties and relate them back to cy
 tidine analogue structure and neighboring base effects.
LOCATION:Pfizer  Lecture Theatre\,  Department of Chemistry
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