Download Advantages of racemic DNA crystallography

Advantages of Racemic DNA Crystallography
Pradeep K. Mandal1, Gavin W. Collie1, Brice Kauffmann2, Ivan Huc1.
1Université
de Bordeaux, CBMN, UMR5248, IECB; 2Université de Bordeaux, UMS3033, IECB
The difficulty of producing well-ordered crystals for X-ray diffraction experiment is recognized
as a major limiting factor for structure determination. Small organic molecules prefer to crystallize in
space group in which it is easiest to fill space. Larger molecules such as biomolecules, crystallizes
primarily in space groups in which it is easiest to achieve connectivity. The strong tendency of racemic
mixtures to yield racemic crystals can be exploited to overcome this difficulty, as racemates increase
the chances of crystallization by allowing molecular contacts to be formed in a greater number of
ways. The prevalence of racemates has been repeatedly verified experimentally over the years to
small molecules [1], helical molecules such as helicates [2] and helical aromatic or aliphatic Foldamers
[3]. The propensity of enantiomers to co-crystallize is so strong that even pseudo-enantiomers
(molecules that are almost but not exactly mirror images) co-crystallize to form so-called quasiracemic crystals.[4] With the advent of protein chemical synthesis, the production of protein racemates
and racemic-protein crystallography has become possible [5,6]. Curiously, racemic DNA
crystallography had not been investigated despite the current commercial availability and affordability
of L- and D-deoxyribo-oligonucleotides. We describe here a systematic study of racemic crystal
structures of various DNA sequences and folded conformations, including duplexes, quadruplexes and
a four-way junction, showing that the advantages of racemic crystallography should extend to DNA as
well.
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