Inhibition of HIV replication using soluble Tat peptide analogs
AssigneeThe United States of America as represented by the Department of Health and Human Resources
InventorsFatah Kashanchi, Mohammad Reza Sadaie, John Brady
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Abstract
Methods and compositions for inhibiting replication of HIV in a mammalian cell. The compositions can be a peptide, or a nucleic acids encoding a peptide, which inhibits transactivation of the HIV long terminal repeat.
Claims8
An isolated transdominant soluble Tat peptide, comprising a transdominant peptide sequence having the sequence Cys-Phe-Xaa39-Xaa40-Xaa41-Gly-Leu-Gly-Ile-Ser-Xaa47-Gly-Xaa49-Lys (SEQ ID NO:1), wherein Xaa39 is an amino acid residue selected from the group consisting of:
- Leu, Met, Ile, Thr, Gln, and Val;
- Xaa40 is an amino acid residue selected from the group consisting of:
- Thr, Arg, Lys, and Asn;
- Xaa41 is an amino acid residue exclusive of Lys;
- Xaa47 is an amino acid residue selected from the group consisting of:
- Tyr and His;
- Xaa49 is an amino acid residues selected from the group consisting of:
- Arg and Lys;
- wherein said peptide sequence comprises at least one amino acid residue substitution, which is an amino acid other than the wild type amino acid, at a position selected from the group consisting of:
- 44, 46, and 47, and wherein the amino acid substitution is an amino acid residue selected from the group consisting of:
- Gly, Ala, Val, Leu, Ile, Pro, Phe, Tyr, Trp, Cys, Met, Ser, Thr, Lys, Arg, His, Asp, Glu, Asn, and Gln;
- and
- wherein said transdominant soluble Tat peptide lacks an intact amino-terminal domain or an intact cysteine-rich domain.
A method of inhibiting human immunodeficiency virus (HIV) replication in a mammalian cell, said method comprising administering a therapeutically effective amount of a transdominant soluble Tat peptide to said mammalian cell, said Tat peptide comprising a transdominant peptide sequence having the sequence Cys-Phe-Xaa39-Xaa40-Xaa41-Gly-Leu-Gly-Ile-Ser-Xaa47-Gly-Xaa49-Lys (SEQ ID NO:1), wherein Xaa39 is an amino acid residue selected from the group consisting of:
- Leu, Met, Ile, Thr, Gln, and Val;
- Xaa40 is an amino acid residue selected from the group consisting of:
- Thr, Arg, Lys, and Asn;
- Xaa41 is an amino acid residue exclusive of Lys;
- Xaa47 is an amino acid residue selected from the group consisting of:
- Tyr and His;
- Xaa49 is an amino acid residues selected from the group consisting of:
- Arg and Lys;
- wherein said peptide sequence comprises at least one amino acid residue substitution, which is an amino acid other than the wild type amino acid, at a position selected from the group consisting of:
- 44, 46, and 47, and wherein the amino acid substitution is an amino acid residue selected from the group consisting of:
- Gly, Ala, Val, Leu, Ile, Pro, Phe, Tyr, Trp, Cys, Met, Ser, Thr, Lys, Arg, His, Asp, Glu, Asn, and Gln;
- and
- wherein said transdominant soluble Tat peptide lacks an intact amino-terminal domain or an intact cysteine-rich domain;
- thereby inhibiting HIV replication.
Dependencies are inferred from the claim text.