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US 11,952,432 B2Granted
Cell-permeable stapled peptide modules for cellular delivery
AssigneeDana-Farber Cancer Institute, Inc.
InventorsLoren D. Walensky, Rida Mourtada, Henry D. Herce
Life of this patent
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Abstract
The disclosure relates to cell-permeable stabilized peptide modules and methods of use for e.g., cellular delivery of cargoes.
Claims24
A fusion polypeptide comprising:
- an internally cross-linked polypeptide comprising any one of the amino acid sequences:
- (i) X1R2R3R2X5R2B (SEQ ID NO:
- 3), (ii) X1R2R3R2X5B (SEQ ID NO:
- 4), (iii) X1R2R2R2X5R2B (SEQ ID NO:
- 7), (iv) X1R2R3R2X4R2BGBR2X5R2R3R2X6 (SEQ ID NO:
- 8), or (v) X1R2R3R2X4R2BGX5R2R3R2X6R2B (SEQ ID NO:
- 9),
- wherein B is Norleucine;
- wherein R2 is L-Arg;
- R3 is D-Arg;
- wherein X1, X4, X5, and X6 are each (S)-2-(4′-pentenyl) alanine;
- wherein X1 and X4 and X5 and X6 are cross-linked, and wherein the internally cross-linked polypeptide is linked to a second moiety.
9 more elements
A compound comprising an internally cross-linked polypeptide comprising any one of the amino acid sequences:
- (i) X1R2R3R2X5R2B (SEQ ID NO:
- 3), (ii) X1R2R3R2X5B (SEQ ID NO:
- 4), (iii) X1R2R2R2X5R2B (SEQ ID NO:
- 7), (iv) X1R2R3R2X4R2BGBR2X5R2R3R2X6 (SEQ ID NO:
- 8), or (v) X1R2R3R2X4R2BGX5R2R3R2X6R2B (SEQ ID NO:
- 9),
- wherein B is Norleucine;
- wherein R2 is L-Arg, R3 is D-Arg;
- wherein X1, X4, X5, and X6 are each (S)-2-(4′-pentenyl) alanine;
- and
- wherein X1 and X4 and X5 and X6 are cross-linked,
- and a cargo.
9 more elements
A method of delivering an agent into a cell, the method comprising:
- contacting the cell with a compound comprising (1) the agent and (2) a cell-permeable stapled peptide, wherein the agent is linked to the cell-permeable stapled peptide, wherein the cell-permeable stapled peptide comprises an internally cross-linked polypeptide comprising any one of the amino acid sequences:
- (i) X1R2R3R2X5R2B (SEQ ID NO:
- 3), (ii) X1R2R3R2X5B (SEQ ID NO:
- 4), (iii) X1R2R2R2X5R2B (SEQ ID NO:
- 7), (iv) X1R2R3R2X4R2BGBR2X5R2R3R2X6 (SEQ ID NO:
- 8), or (v) X1R2R3R2X4R2BGX5R2R3R2X6R2B (SEQ ID NO:
- 9),
- wherein B is Norleucine;
- wherein R2 is L-Arg, R3 is D-Arg;
- wherein X1, X4, X5, and X6 are each (S)-2-(4′-pentenyl) alanine;
- and
- wherein X1 and X4 and X5 and X6 are cross-linked.
9 more elements
A method of administering an agent to a subject, the method comprising:
- administering to a subject in need thereof a compound comprising (1) the agent and (2) a cell-permeable stapled peptide, wherein the agent is linked to the cell-permeable stapled peptide, wherein the cell-permeable stapled peptide comprises an internally cross-linked polypeptide comprising any one of the amino acid sequences:
- (i) X1R2R3R2X5R2B (SEQ ID NO:
- 3), (ii) X1R2R3R2X5B (SEQ ID NO:
- 4), (iii) X1R2R2R2X5R2B (SEQ ID NO:
- 7), (iv) X1R2R3R2X4R2BGBR2X5R2R3R2X6 (SEQ ID NO:
- 8), or (v) X1R2R3R2X4R2BGX5R2R3R2X6R2B (SEQ ID NO:
- 9),
- wherein B is Norleucine;
- wherein R2 is L-Arg, R3 is D-Arg;
- wherein X1, X4, X5, and X6 are each (S)-2-(4′-pentenyl) alanine;
- and
- wherein X1 and X4 and X5 and X6 are cross-linked.
9 more elements
An internally cross-linked polypeptide comprising any one of the amino acid sequences:
- (i) X1R2R3R2X5R2B (SEQ ID NO:
- 3), (ii) X1R2R3R2X5B (SEQ ID NO:
- 4), (iii) X1R2R2R2X5R2B (SEQ ID NO:
- 7), (iv) X1R2R3R2X4R2BGBR2X5R2R3R2X6 (SEQ ID NO:
- 8), or (v) X1R2R3R2X4R2BGX5R2R3R2X6R2B (SEQ ID NO:
- 9),
- wherein B is Norleucine;
- wherein R2, is L-Arg;
- R3 is D-Arg;
- wherein X1, X4, X5, and X6 are each (S)-2-(4′-pentenyl) alanine;
- and
- wherein X1 and X4 and X5 and X6 are cross-linked.
9 more elements
Dependencies are inferred from the claim text.