Nucleic Acids Research, Vol 27, Issue 23 4632-4635, Copyright © 1999 by Oxford University Press
OA Amosova and JR Fresco
Eight base analogs were tested as third strand residues in otherwise
homopyrimidine strands opposite each of the 'direct' (A.T and G.C) and
'inverted' (T.A and C.G) Watson-Crick base pairs, using UV melting profiles
to assess triplex stability. The target duplexes contained 20 A.T base
pairs and a central test base pair X.Y, while the third strand contained 20
T residues and a central Z test base. Z included 5-bromo- uracil,
5-propynyluracil, 5-propynylcytosine, 5-methyl-cytosine, 5- bromocytosine,
hypoxanthine, 2-amino-purine and 2,6-diaminopurine. Some of the base
analogs enhanced third strand binding to the target duplex with one or
other 'inverted' central base pair relative to the binding afforded by any
of the canonical bases. Other analogs did the same for the duplexes with
the 'direct' target pairs. The increasing order of triplex stabilization by
these base analogs is: opposite the 'inverted' base pairs, for T.A, A <
C < 5-pC < 5-pU < T < 5-BrC < 5-meC < 5-BrU < 2-AP
< 2,6-DAP < Hy < G, for C.G, 2-AP < A < Hy < G < 5-pC
< 5-BrC < 5- meC < C < 2,6-DAP < T < 5-BrU < 5-pU;
opposite the 'direct' base pairs, for A.T, 2-AP < A < 5-meC < C
< G < Hy < 2,6-DAP < 5-pU < T = 5-BrU < 5- BrC < 5-pC,
for G.C, G < 2,6-DAP < 2-AP < A < Hy < T < 5-BrU <
5-pU < 5- pC < 5-BrC < C < 5-meC.
ARTICLES
A search for base analogs to enhance third-strand binding to 'inverted' target base pairs of triplexes in the pyrimidine/parallel motif
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
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