Jun C Kim

US Patent:

20150266936, Sep 24, 2015

Filed:

Oct 18, 2013

Appl. No.:

14/435711

Inventors:

- Stanford CA, US
Jun Woo Kim - Fullerton CA, US
Frank V. Cochran - Stanford CA, US

International Classification:

C07K 14/47
A61K 47/48
C07K 14/81

Abstract:

Disclosed are knottin peptides containing non-natural amino acids so that they can be formed by chemical conjugation into two or more knottin monomers. The knottin monomers comprise a non-natural amino acid such as an aminooxy residue within the polypeptide sequence. The exemplified dimers were produced by oxime formation between two aldehyde groups present on a polyether linker and an aminooxy functional group that was site-specifically incorporated the knottin. Knottins variants based on EETI (trypsin inhibitor) and AgRP (Agouti-related protein) were engineered to contain integrin-binding loops. These dimers were shown to have increased binding strength to integrins on U87MG tumor cells, achieving significant increases in inhibition of cell adhesion and proliferation. Also disclosed are knottin monomers comprising an aminooxy residue; these may be conjugated to molecules such as doxorubicin.