Selective αvβ3 receptor peptide antagonist for therapeutic and diagnostic applications
AssigneeAdvanced Accelerator Applications SA
InventorsAnnarita Del Gatto, Laura Zaccaro, Carlo Pedone, Michele Saviano
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Abstract
The present invention is related to new peptide antagonists of αvβ3 receptor, designed on the basis of the crystal structure of integrin αvβ3 in complex with c(RGDf[NMe]V) and the NMR structure of echistatin. These peptides are potent and selective antagonists of the αvβ3 receptor and can be used as novel anticancer drugs and/or new class of diagnostic non-invasive tracers as suitable tools for αvβ3-targeted therapy and imaging.
Claims11
An antagonist compound of αvβ3 integrin, displaying a selective affinit for αvβ3 integrin, containing a cyclic RGD motif and two echistatin C-terminal moieties covalently linked by a spacer sequence having the following formula (I):
- wherein:
- AA1 is an alpha amino acid selected in the group of Cys, Asp, Glu, Lys, Orn, Pen, Dab or Dap;
- AA2 is an alpha amino acid selected in the group of Cys, Asp, Glu, Lys, Orn, Pen, Dab or Dap;
- L is a linker sequence consisting of a number of amino acid residues comprised between 0 and 2, such as the sequence PG;
- (Xaa)n is an amino acid sequence in which n ranges from 1 to 3, which sequence is substantially homologue to that of sequence 28-30 of Echistatin:
- MDD
- (Yaa)m is an amino acid sequence in which m ranges from 2 to 9, which sequence is substantially homologue to that of C-terminus (41-49) of Echistatin:
- RNPHKGPAT(SEQ ID NO:3).
An antagonist compound of αvβ3 integrin, displaying a selective affinity for αvβ3 integrin, containing a pentapeptide cyclic RGD motif and two echistatin C-terminal moieties covalently linked by a spacer sequence.
Dependencies are inferred from the claim text.