US 7,501,503 B2
Compositions and methods for inhibiting RNase H activity of retroid reverse transcriptase
Masad J. Damha, St. Hubert (Canada); Rami N. Hannoush, Cambridge, Mass. (US); Kyung-Lyum Min, Montreal (Canada); and Sandra Carriero, St. Lazare (Canada)
Assigned to McGill University, Montreal QC (Canada)
Filed on Dec. 30, 2003, as Appl. No. 10/748,475.
Claims priority of provisional application 60/509716, filed on Oct. 07, 2003.
Claims priority of provisional application 60/437568, filed on Dec. 31, 2002.
Prior Publication US 2004/0138166 A1, Jul. 15, 2004
Int. Cl. C07H 21/04 (2006.01)
U.S. Cl. 536—24.5  [536/23.1; 536/24.33] 1 Claim
 
1. A composition for inhibiting the RNase H activity of a retroid virus reverse transcriptase comprising an inhibitory agent of Formula I:

OG Complex Work Unit Drawing
wherein,
X1 and X2 are antiparallel complementary oligonucleotide strands that associate to form a duplex;
X1 is 2 to 24 nucleotides in length;
X2 is 2 to 24 nucleotides in length;
Y1 is 2 to 8 nucleotides in length;
Y2 is 2 to 8 nucleotides in length;
at least one of Y1 or Y2 is 4 to 8 nucleotides in length;
Y1 and Y2 each independently contain a ribonucleic acid; 2′,5′-linked ribonucleic acid; or combination thereof wherein a Y1 or Y2 of at least 4 nucleotides comprises the sequence 5′-UUYG-3′/2′ (SEQ ID NO:1);
wherein the inhibitory agent comprises the nucleotide sequence set forth in SEQ ID NO:2; and
wherein the inhibitory agent binds to the RNase H domain of retroid virus reverse transcriptase thereby inhibiting the RNase H activity thereof.