Acid-Induced Exchange of the Imino Proton in G.C Pairs
Résumé
Acid-induced catalysis of imino proton exchange inG.C pairs of DNA duplexes is surprisingly fast, beingnearly as fast as for the isolated nucleoside, despitebase-pair dissociation constants in the range of 10–5 atneutral or basic pH. It is also observed in terminal G.Cpairs of duplexes and in base pairs of drug–DNAcomplexes. We have measured imino proton exchangein deoxyguanosine and in the duplex d(ATATAGATC-TATAT) as a function of pH. We show that acid-inducedexchange can be assigned to proton transfer fromN7-protonated guanosine to cytidine in the open stateof the pair. This is faster than transfer from neutralguanosine (the process of intrinsic catalysis previous-ly characterized at neutral pH) due to the lower iminoproton pK of the protonated form, 7.2 instead of 9.4.Other interpretations are excluded by a study ofexchange catalysis by formiate and cytidine as ex-change catalysts. The cross-over pH between theregimes of pH-independent and acid-induced ex-change rates is more basic in the case of base pairsthan in the mononucleoside, suggestive of an increaseby one to two decades in the dissociation constant ofthe base pair upon N7 protonation of G. Acid-inducedcatalysis is much weaker in A.T base pairs, as expectedin view of the low pK for protonation of thymidine.
Domaines
Biologie structurale [q-bio.BM]Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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