Tuesday, July 17, 2007

Tautomers of Adenine, Cytosine, Guanine, and Thymine

 
The four bases of DNA can exist in at least two tautomeric forms as shown below. Adenine and cytosine (which are cyclic amidines) can exist in either
amino or imino forms, and guanine, thymine, and uracil (which are cyclic amides) can exist in either lactam (keto) or lactim (enol) forms. The tautomeric forms of each base exist in equilibrium but the amino and lactam tautomers are more stable and therefore predominate under the conditions found inside most cells. The rings remain unsaturated and planar in each tautomer.


Fifty years ago it wasn't clear whether the amino or imino forms of the purines were stable under physiological conditions. (Or the lactam lactim forms.) As we will see, this uncertainty played a significant role in events leading up to the discovery of the structure of DNA.

We now know that all of the bases in the common nucleotides can participate in hydrogen bonding. The amino groups of adenine and cytosine are hydrogen donors, and the ring nitrogen atoms (N-1 in adenine and N-3 in cytosine) are hydrogen acceptors (see below). Cytosine also has a hydrogen acceptor group at C-2. Guanine, cytosine, and thymine can form three hydrogen bonds. In guanine, the group at C-6 is a hydrogen acceptor, and N-1 and the amino group at C-2 are hydrogen donors. In thymine, the groups at C-4 and C-2 are hydrogen acceptors, and N-3 is a hydrogen donor. (Only two of these sites, C-4 and N–3, are used to form base pairs in DNA.) The hydrogen-bonding patterns of bases have important consequences for the three-dimensional structure of nucleic acids.



©Laurence A. Moran and Pearson/Prentice Hall 2007

11 comments :

  1. This helped me with my medicinal homework... Thank you!

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  2. thanks this helped me under stand proofreading by DNA polymerase where a tautomeric form of C base pairs with A

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  3. thank u very much. this is very useful to me to understand the tautomerism of this molecules

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  4. thank you very much. this article helps me understanding toutomeric form of bases of DNA.

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  5. Professor Sandwalk, I have these isoforms of cytosine drawn. Based on the structure and H-donor and acceptor roles, however, I could not figure out how is that going to contribute to the C->A mismatch? Coudl you help me? Thanks!

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  6. Very helpful! Clear and easily understandable, without being condescending - a relief! Thanks

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  7. Thanks!
    But I have a question which is > Is the tautomeric form still remains aromatic? If not how it is possible that the stable aromatic ring changes its structure to form a tautomer?

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  8. Hi I was wondering is there a specific reason why one tautomeric form is more stable than the other in terms of the physiological environments the bases are exposed to? If so could you explain some of those factors that lead to one tautomeric form being more favourable than the other.

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  9. have you used mulliken atomic charge, HOMO-LUMO and band gap datas? they infered that the N1 7 tautomer is more stable that the enol form. The enol form may be in equilibrium with the N1 7 that N1 9 form

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  10. Hi Larry. I'm new to this field, but your comment on this would be appreciated. Do both the imine and enol forms of the Bases A,G,C,T exist in the cytoplasm? And, if so, do you know why the model for DNA mutation proposed by Per-Olov Lowdin in 1963 (Proton Tunneling in DNA and its Biological Implications) didn't have more impact? He proposed that proton tunneling turned base combinations like A-C into a 1/2 enol pair A*-C (where * represents the enol form). Upon splitting, the A* produced another A*-C, but the C then joined with G to form C-G, essentially turning the original A-base code into a G-base.

    [to clarify this inquiry: why is this model not the explanation for the source of cancer?]

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  11. Can you tell me the name of the compound which exhibits tautomerism, but does not exhibit hydrogen migration?

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