Method of modulating integrin mediated cellular activity and agents useful for same
AssigneeInter-K Pty Limited
InventorsMichael Valentine Agrez, Nuzhat Ahmed
Life of this patent
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Abstract
There is disclosed agents capable of inhibiting the binding of a MAP kinase to a binding domain of an integrin for the MAP kinase, and methods of modulating the activity of a cell utilizing the agents. The methods are particularly suitable for inhibiting the growth of cancer cells.
Claims26
A polypeptide for inhibiting growth of a cancer cell, the polypeptide comprising an amino acid sequence selected from the group consisting of 1) an amino acid sequence defining a binding domain of a β integrin subunit for ERK2 MAP kinase, said binding domain comprising an intervening, centrally located amino acid linker sequence that links opposite terminal end amino acid sequence regions of the binding domain together and is non-essential for binding of the MAP kinase to the binding domain, the amino acid sequence defining the binding domain being selected from the group consisting of RSKAKWQTGTNPLYR (SEQ ID NO. 2), RARAKWDTANNPLYK (SEQ ID NO. 22) and RSRARYEMASNPLYR (SEQ ID NO. 23);
- and 2) an amino acid sequence defining the binding domain as specified in 1) wherein the linker sequence of the binding domain is deleted such that the opposite terminal end amino acid sequence regions of the binding domain remain and are contiguous with one another in the polypeptide, and the polypeptide is from 10 to 15 amino acids in length.
An agent for inhibiting growth of a cancer cell, the agent comprising a polypeptide coupled to a facilitator moiety for facilitating passage of the polypeptide across the outer cell membrane of the cancer cell into the cancer cell, and the polypeptide having an amino acid sequence selected from the group consisting of 1) an amino acid sequence defining a binding domain of a β integrin subunit for ERK2 MAP kinase, said binding domain comprising an intervening, centrally located amino acid linker sequence that links opposite terminal end amino acid sequence regions of the binding domain together and is non-essential for binding of the MAP kinase to the binding domain, the amino acid sequence defining the binding domain being selected from the group consisting of RSKAKWQTGTNPLYR (SEQ ID NO. 2), RARAKWDTANNPLYK (SEQ ID NO. 22) and RSRARYEMASNPLYR (SEQ ID NO. 23);
- and 2) an amino acid sequence defining the binding domain as specified in 1) wherein the linker sequence of the binding domain is deleted such that the opposite terminal end amino acid sequence regions of the binding domain remain and are contiguous with one another in the polypeptide, and the polypeptide is from 10 to 25 amino acids in length.
A polypeptide for inhibiting growth of a cancer cell, the polypeptide comprising an amino acid sequence of a binding domain of a β integrin subunit for ERK2 MAP kinase, the binding domain including an intervening, centrally located amino acid linker sequence that links opposite terminal end amino acid sequence regions of the binding domain together and is non-essential for binding of the MAP kinase to the binding domain, the binding domain being defined by a peptide selected from the group consisting of RSKAKWQTGTNPLYR (SEQ ID NO. 2), RARAKWDTANNPLYK (SEQ ID NO. 22) and RSRARYEMASNPLYR (SEQ ID NO. 23), wherein the linker sequence of the binding domain is deleted in the polypeptide such that the opposite terminal end amino acid sequence regions of the binding domain remain and are contiguous with one another in the polypeptide.
Dependencies are inferred from the claim text.