DNA chemistry

Bill Melchior, NCTR/FDA WMELCHIOR at NTET.NCTR.FDA.GOV
Thu Jul 16 09:50:33 EST 1992


Several messages, both to the list and to me have suggested that I
underestimated, yesterday, the desire for basic information by list
members.  With that in mind, a couple of additional comments on DNA
chemistry.

A book that explains LOTS about nucleic acids is Wolfram Saenger's 
"Principles of Nucleic Acid Structure" (Springer-Verlag; 1984): 
structure, stability, hydrogen bonding, pH effects, etc.

pp 62-65 give a discussion of the reasons for RNA being different.
(RNA adopts only the A and A' conformations; it cannot go to the
B and Z families of conformation.  In other words, the sugar pucker
is always C3'-endo in RNA, while in B form DNA it is C2'-endo.  Free
ribonucleosides, however, can readily adopt the C3'-endo pucker.)
Saenger discusses hydrogen bonding and steric effects as possible
causes and then ends by saying, "In summary, the forces determining
the C3'-endo stabilization of RNA secondary structure remain unclear,
and probably several factors contribute."  (Note that RNA DOES form
double stranded structures.  For example, tRNAs are mostly helical;
and many other RNAs have extensive helical regions.)

I'd like also to add a comment to Scott Keeney's lesson in bonding.
Hydrophobic bonds are frequently misunderstood.  The important factor
is the energy of the total system; solvent + solute.  A simple salt
(eg NaCl) may not interact with a macromolecule at all, but decrease
its solubility by increasing the interaction between water molecules.
In other words, making water-water interactions stronger means that 
the total system has a lower energy if cavities in the structured
solvent to not have to be made in order to accomodate the macro-
molecule.  Thus the common phenomenon of "salting out" a protein
is not proof that the salt interacts with the protein.

The physical chemistry of solubility and intramolecular bonding is
quite complex.  Consider, for instance, the interesting effect of
tetraethylammonium chloride on DNA stability.  As the concentration
is increased, the relative stabilities of AT and GC basepairs get
closer, until at 2.4 M they are identical; at this concentration,
the melting curves of a complex DNA like calf thymus and a simple 
DNA like T7 phage are essentially identical; both melt over a range
of only a degree or two, while in NaCl or Na phosphate, calf thymus
has a melting range of > 10 degrees.



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