Galectin-1/ galectin-3 chimeras and multivalent proteins
View Patent ↗Described herein are Galectin-1/Galectin-3 multivalent protein complexes and uses thereof. In some aspects, Galectin-1/Galectin-3 multivalent protein complexes are useful to treat inflammatory conditions in a subject.
1 . A Galectin-1/Galectin-3 (Gal-1/Gal-3) dimer comprising:
two monomer polypeptides, wherein each monomer polypeptide comprises:
a Galectin-1 (Gal-1) polypeptide;
a Galectin-3 (Gal-3) polypeptide; and
a linker comprising an alpha helix coil, wherein the alpha helix coil comprises the sequence of SEQ ID NO: 9, wherein the linker is fused between the Gal-1 polypeptide and the Gal-3 polypeptide,
wherein the two monomer polypeptides associate with each other via dimerization at the alpha helix coils to form the Gal-1/Gal-3 dimer, wherein one or both of the monomer polypeptides has a sequence that is about 90% to about 100% identical to SEQ ID NO: 3.
2 . The Gal-1/Gal-3 dimer of claim 1 , wherein the Gal-1 polypeptide has a sequence that is about 80% to about 100% identical to SEQ ID NO: 1.
3 . The Gal-1/Gal-3 dimer of claim 1 , wherein the Gal-3 polypeptide has a sequence that is about 80% to about 100% identical to SEQ ID NO: 4.
4 . The Gal-1/Gal-3 dimer of claim 1 , wherein the alpha helix coil has a sequence that is about 80% to about 100% identical to SEQ ID NO: 5.
5 . A pharmaceutical formulation comprising:
the Galectin-1/Galectin-3 (Gal-1/Gal-3) dimer of claim 1 ; and
a pharmaceutically acceptable carrier.
6 . A Galectin-1/Galectin-3 (Gal-1/Gal-3) polypeptide capable of dimerizing comprising:
a Galectin-1 (Gal-1) polypeptide;
a Galectin-3 (Gal-3) polypeptide; and
a linker comprising an alpha helix coil, wherein the alpha helix coil comprises the sequence of SEQ ID NO: 9, wherein the linker is fused between the Gal-1 polypeptide and the Gal-3 polypeptide, wherein the Gal-1/Gal-3 polypeptide has a sequence that is about 90% to about 100% identical to SEQ ID NO: 3.
7 . The Galectin-1/Galectin-3 (Gal-1/Gal-3) dimer of claim 1 , wherein:
(i) the Gal-1 polypeptide in at least one of the monomer polypeptides comprises the sequence of SEQ ID NO: 1;
(ii) the linker in at least one of the monomer polypeptides comprises the sequence of any one of SEQ ID NOs: 5, 10, or 11;
and/or
(iii) at least one of the monomer polypeptides does not comprise an N-terminal tag or a C-terminal tag.
8 . A pharmaceutical formulation comprising:
a plurality of the Galectin-1/Galectin-3 (Gal-1/Gal-3) polypeptide of claim 6 ; and
a pharmaceutically acceptable carrier.
9 . The Gal-1/Gal-3 polypeptide of claim 6 , wherein the Gal-1 polypeptide has a sequence that is about 80% to about 100% identical to SEQ ID NO: 1.
10 . The Gal-1/Gal-3 polypeptide of claim 6 , wherein the Gal-3 polypeptide has a sequence that is about 80% to about 100% identical to SEQ ID NO: 4.
11 . The Gal-1/Gal-3 polypeptide of claim 6 , wherein the alpha helix coil has a sequence that is about 80% to about 100% identical to SEQ ID NO: 5.
12 . The Galectin-1/Galectin-3 (Gal-1/Gal-3) polypeptide of claim 6 , wherein:
(i) the Gal-1 polypeptide comprises the sequence of SEQ ID NO: 1;
(ii) the linker comprises the sequence of any one of SEQ ID NOs: 5, 10, or 11;
and/or
(iii) the Gal-1/Gal-3 polypeptide does not comprise an N-terminal tag or a C-terminal tag.
13 . A Galectin-1/Galectin-3 (Gal-1/Gal-3) polynucleotide comprising:
a polynucleotide that encodes a Galectin-1 (Gal-1) polypeptide;
a polynucleotide that encodes a Galectin-3 (Gal-3) polypeptide; and
a polynucleotide that encodes a linker comprising an alpha helix coil, wherein the alpha helix coil comprises the sequence of SEQ ID NO: 9, wherein the polynucleotide that encodes the alpha helix coil is fused in-frame between the polynucleotide that encodes the Gal-1 polypeptide and the polynucleotide that encodes the Gal-3 polypeptide, wherein the Gal-1/Gal-3 polynucleotide encodes a polypeptide having a sequence that is about 90% to about 100% identical to SEQ ID NO: 3.
14 . The Gal-1/Gal-3 polynucleotide of claim 13 , wherein the Gal-1 polypeptide has a sequence that is about 80% to about 100% identical to SEQ ID NO: 1.
15 . The Gal-1/Gal-3 polynucleotide of claim 13 , wherein the Gal-3 polypeptide has a sequence that is about 80% to about 100% identical to SEQ ID NO: 4.
16 . The Gal-1/Gal-3 polynucleotide of claim 13 , wherein the alpha helix coil has a sequence that is about 80% to about 100% identical to SEQ ID NO: 5.
17 . A vector comprising:
the Gal-1/Gal-3 polynucleotide of claim 13 .
18 . A bacterial cell comprising:
the polynucleotide sequence of claim 13 .
19 . A method for reducing inflammation comprising: administering the Galectin-1/Galectin-3 (Gal-1/Gal-3) dimer of claim 1 or a pharmaceutical formulation comprising the Galectin-1/Galectin-3 (Gal-1/Gal-3) dimer of claim 1 to a subject in need thereof.