Peptides and antibodies that inhibit integrin-ligand binding
AssigneeThe Scripps Research Institute
InventorsEdward F. Plow, Stanley E. D'Souza, Mark H. Ginsberg
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Abstract
Polypeptides which are derived from the Arg-Gly-Asp (RGD) binding portion of an Integrin beta subunit are disclosed as are their use for modulation of Integrin ligand binding. Anti-antibody peptides, hybridomas secreting these antibodies, as well as methods of making any using such antibodies, and recombinant DNA molecules that define the structural gene coding for the polypeptides are also contemplated within the scope of the present invention.
Claims12
A polypeptide of 60 to 90 amino acid residues in length having a sequence homologous to the GPIIIa amino acid residue sequence represented by the formula:
- DYPVDIYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFGAFVDKPVSPYMYISPPE.
A polypeptide corresponding in amino acid residue sequence to the formula:
- a) DYPVIDYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFGAFVDKPVSPYMYISPPE,
- b) GYPIDLYYLMDLSYSMLDDLRNVKKLGGDLLRALNEITESGRIGFGSFVDKTVLPFVNTHP, or
- c) DYPIDLYYLMDLSYSMKDDLENVKSLGTDLMNEMRRITSDFRIGFGSFVEKTVMPYISTTP.
The recominant DNA molecule of claim 5 wherein said structural gene codes for a polypeptide according to claim 2.
A nucleotide segment containing no more than 12,000 nucleotide base pairs including a sequence defining a structural gene coding for a polypeptide of 60 to 90 amino acid residues in length having a sequence homologous to the GPIIIa amino acid residue sequence represented by the formula:
- DYPVDIYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFGAGVDKPVSPYMYISPPE, wherein said structural gene sequence contains no more than 2,000 base pairs.
A monoclonal antibody comprising antibody molecules that immunoreact with a) GPIIIa, and b) a polypeptide corresponding to the formula:
- DYPVDIYYLMDLSYSMKDDLWSIQNLGTKLATQMRKLTSNLRIGFGAFVDKPUSPYMYISPPE.
A monoclonal antibody comprising antibody molecules that immunoreact with a) the beta subunit of the LeuCam Integran and b) a polypeptide corresponding to the formula:
- GYPIDLYYLMDLSYSMLDDLRNVKKLGGDLLRALNEITESGRIGFGSFVDKTVLPFVNTHP.
A monoclonal antibody comprising antibody molecules that immunoreact with a) the beta subunit of the VLA Integran, and b) a polypeptide corresponding to the formula:
- DYPIDLYYLMDLSYSMKDDLENVKSLGTDLMNEMRRITSDRFIGFGSFVEKTVMPYISTTP.
Dependencies are inferred from the claim text.