The Design of Oligonucleotides Which Attack Specific Gene Targets.
Final rept. 1 Dec 88-30 Nov 91,
BAYLOR COLL OF MEDICINE THE WOODLANDS TX CENTER FOR BIOTECHNOLOGY
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Triple Helix Design Principles. The first research priority of the program of Navy support was to refine our understanding of triple helix forming oligonucleotides TFOs. Binding affinity and strand orientation of triplex forming oligonucleotides were measured as a function of base composition. Based upon that work, which was published in Biochemistry ref. 3, we showed that triple helices containing GGC and TAT triplets were stable at physiological pH and prefer to bind with an antiparallel strand orientation. This study and the accompanying patent application provided the first evidence that TFOs can bind in a site selective fashion at physiological pH and the first explicit evidence for a new antiparallel class of triple helix. This work also served as the basis for the filing of a continuation in part to a patent application, filed 12 89. DNA Recognition, Triple helix formation.
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