Soluble chimeric peptide inhibitors of HIV entry comprising an IZ trimeric coiled-coil peptide and HIV gp41 N-helix coiled-coil peptide
View Patent ↗Described herein are chimeric peptides comprising a soluble trimeric coiled-coil and all or a portion of the N-peptide region of HIV gp41. These molecules are stable, trimeric coiled-coils that inhibit HIV entry into cells, such as human cells. Such peptides can be further assessed to demonstrate their ability to serve as potent anti-HIV therapeutic molecules and thus, as therapeutic molecules or drugs.
1. A soluble trimeric coiled-coil peptide comprising an isoleucine zipper (IZ) trimeric coiled-coil peptide and a portion of the HIV gp41 N-helix coiled-coil, wherein the portion of the HIV gp41 N-helix coiled-coil binds to the C-peptide region of HIV gp41.
2. The soluble trimeric coiled-coil peptide of claim 1 , wherein the isoleucine zipper (IZ) trimeric coiled-coil peptide comprises an amino acid sequence selected from the group consisting of: YGGIKKEIEAIKKEQEAIKKKIEAIEKEIEA (SEQ ID NO: 11); YGGIEKKIEAIEKKIEAIEKKIEAIEKKIEA (SEQ ID NO: 16); or amino acids 1-24 of SEQ ID NO: 31.
3. The soluble trimeric coiled-coil peptide of claim 1 , wherein the portion of the HIV gp41 N-helix coiled-coil comprises the amino acid sequence: LLXLTVWGXKXLQXRXX (SEQ ID NO: 28), wherein amino acid residues L, T, V, W, G, K, Q, and R are the single letter code used for amino acid residues and X can be any amino acid residue.
4. The soluble trimeric coiled-coil peptide of claim 3 , wherein the amino acid sequence of the portion of the HIV gp41 N-helix coiled-coil is selected from the group consisting of: SEQ ID NO: 18, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 34, and SEQ ID NO: 35.
5. The soluble trimeric coiled-coil peptide of claim 1 , wherein the amino acid sequence of the soluble trimeric coiled-coil peptide is selected from the group consisting of IZN17 (SEQ ID NO: 31), IZN23 (SEQ ID NO: 32), or IZN36 (SEQ ID NO: 33).
6. A soluble trimeric coiled-coil comprising a peptide IQN36, wherein the amino acid sequence of IQN36 is:
RMKQIEDKIEEIESKQKKIENEIARIKKLISGIVQQQNNLLRAIEAQQHLLQLTVWG IKQLQARIL (SEQ ID NO: 4).
7. A soluble trimeric coiled-coil consisting of a peptide IQN36, wherein the amino acid sequence of IQN36 is:
RMKQIEDKIEEIESKQKKIENEIARIKKLISGIVQQQNNLLRAIEAQQHLLQLTVWG IKQLQARIL (SEQ ID NO: 4).
8. A soluble trimeric coiled-coil comprising a peptide IZN36, wherein the amino acid sequence of IZN36 is:
IKKEIEAIKKEQEAIKKKIEAIEKEISGIVQQQNNLLRAIEAQQHLLQLTVWGIKQL QARIL (SEQ ID NO: 33).
9. A soluble trimeric coiled-coil consisting of a peptide IZN36, wherein the amino acid sequence of IZN36 is:
IKKEIEAIKKEQEAIKKKIEAIEKEISGIVQQQNNLLRAIEAQQHLLQLTVWGIKQL QARIL (SEQ ID NO: 33).