| CPC A61K 35/17 (2013.01) [C07K 14/7051 (2013.01); C07K 14/70517 (2013.01); C07K 14/70521 (2013.01); C07K 14/775 (2013.01); A61K 38/00 (2013.01); C07K 2319/70 (2013.01)] | 20 Claims |
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1. A ligand regulated protein-protein interaction system comprising:
(a) a lipocalin-fold molecule;
(b) a lipocalin-fold ligand with a low molecular weight of 1500 Da or below; and
(c) a lipocalin-fold binding interaction partner;
wherein the lipocalin-fold molecule can bind to the lipocalin-fold ligand; and
wherein the lipocalin-fold molecule bound to the lipocalin-fold ligand binds to the lipocalin-fold binding interaction partner with an affinity which is at least 10-fold higher than the affinity of the lipocalin-fold molecule not bound to the lipocalin-fold ligand;
and wherein the lipocalin-fold binding interaction partner is not a naturally occurring protein which has an affinity of <10 μM to any naturally occurring lipocalin-fold molecule in the presence of any lipocalin-fold ligand,
wherein the lipocalin-fold molecule is a lipocalin or a derivative thereof with 1-30 amino acid exchanges and/or 1-50 amino acid deletions and/or 1-50 amino acid insertions,
wherein the lipocalin-fold molecule is a derivative of a naturally occurring lipocalin with at least 70% sequence identity in the β-barrel structure, whereby this β-barrel structure is defined as the regions corresponding structurally to the regions of amino acid residues selected from
amino acid residues 21-30, 41-47, 52-58, 71-78, 85-88, 102-109, 114-120 and 132-138 in human RBP4 according to the amino acid residue numbering scheme in the PDB entry 1RBP, which define the structurally conserved ß-strands in human RBP4; and
amino acid residues 14-23, 37-43, 48-54, 62-69, 76-79, 84-91, 96-102 and 111-117 in human tear lipocalin (TLC), which define the structurally conserved ß-strands in human TLC.
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