Stablized EZH2 peptides
AssigneeDana-Farber Cancer Institute, Inc.
InventorsLoren D. Walensky, Gregory H. Bird, Woojin Kim, Stuart Orkin
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Abstract
Provided herein are polypeptides containing stabilized therapeutic peptides related to enhancer of zeste homolog 2 (EZH2), histone lysine N-methyltransferase. Also provided are compositions containing these polypeptides and methods of using such peptides in the treatment of cancer that include administering to a subject one of the polypeptides.
Claims43
An internally cross-linked polypeptide that inhibits the interaction between Enhancer of Zeste Homolog 2 (EZH2) and Embryonic Ectoderm Development (EED), the internally cross-linked polypeptide comprising the amino acid sequence FSSNRX1KILX2RTEILNQEWKQRRIQPV (SEQ ID NO:26), wherein X1 and X2 are each a non-natural amino acid with an olefinic side chain, and wherein the internally cross-linked polypeptide is cell penetrant.
An internally cross-linked polypeptide that inhibits the interaction between Enhancer of Zeste Homolog 2 (EZH2) and Embryonic Ectoderm Development (EED), the internally cross-linked polypeptide comprising the amino acid sequence FSSNRX1KILX2RTQILNQEWKQRRIQPV (SEQ ID NO:27), wherein X1 and X2 are each a non-natural amino acid with an olefinic side chain, and wherein the internally cross-linked polypeptide is cell penetrant.
An internally cross-linked polypeptide that inhibits the interaction between Enhancer of Zeste Homolog 2 (EZH2) and Embryonic Ectoderm Development (EED), the internally cross-linked polypeptide comprising the amino acid sequence FSSNRX1KILX2RTX3ILNX4EWKQRRIQPV (SEQ ID NO:
- 56), wherein X1, X2, X3, and X4 are each a non-natural amino acid with an olefinic side chain, and wherein the internally cross-linked polypeptide is cell penetrant.
An internally cross-linked polypeptide that inhibits the interaction between Enhancer of Zeste Homolog 2 (EZH2) and Embryonic Ectoderm Development (EED), the internally cross-linked polypeptide comprising an amino acid sequence set forth in FSSNRX1KILX2RTEILNQEWKQRRIQPV (SEQ ID NO:26), except that one or more amino acids at positions 2, 3, 9, 13, 14, 17, 21 or 23 of SEQ ID NO:
- 26 are substituted, and wherein X1, and X2, are each a non-natural amino acid with an olefinic side chain, and wherein the internally cross-linked polypeptide is cell penetrant.
Dependencies are inferred from the claim text.