Protein scaffolds for antibody mimics and other binding proteins
First Claim
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1. A non-antibody protein comprising a domain having an immunoglobulin-like fold, said non-antibody protein deriving from a reference protein having an immunoglobulin-like fold by having a mutated amino acid sequence, wherein said domain having an immunoglobulin-like fold has a sequence that is at least 80% identical to the seciuence of SEQ ID NO:
- 81 and, wherein said non-antibody protein binds with a Kd at least as tight as 1 μ
M to a compound that is not bound as tightly by said reference protein.
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Abstract
Disclosed herein are proteins that include an immunoglobulin fold and that can be used as scaffolds. Also disclosed herein are nucleic acids encoding such proteins and the use of such proteins in diagnostic methods and in methods for evolving novel compound-binding species and their ligands.
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Citations
33 Claims
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1. A non-antibody protein comprising a domain having an immunoglobulin-like fold, said non-antibody protein deriving from a reference protein having an immunoglobulin-like fold by having a mutated amino acid sequence, wherein said domain having an immunoglobulin-like fold has a sequence that is at least 80% identical to the seciuence of SEQ ID NO:
- 81 and, wherein said non-antibody protein binds with a Kd at least as tight as 1 μ
M to a compound that is not bound as tightly by said reference protein. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
- 81 and, wherein said non-antibody protein binds with a Kd at least as tight as 1 μ
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25. A method of obtaining a derivative non-antibody protein which binds to a compound, said method comprising:
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(a) providing a non-antibody scaffold protein comprising a domain having an immunoglobulin-like fold, wherein said scaffold protein does not bind to said compound with a Kd as tight as 1 μ
M;(b) generating mutated derivatives of said non-antibody scaffold protein wherein said derivatives comprise a domain having an immunoglobulin-like fold and a sequence that is at least 80% identical to the sequence of SEQ ID NO;
81, thereby producing a library of mutated proteins;(c) contacting said library with said compound; (d) selecting from said library at least one derivative protein which binds to said compound with a Kd at least as tight as 1 μ
M; and(e) optionally repeating steps (b)–
(d) substituting for the non-antibody scaffold protein in repeated step (b) the product from the previous step (d).
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26. A method for obtaining a non-antibody protein which binds to a compound, said method comprising:
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(a) contacting said compound with a candidate protein, said candidate protein being a derivative non-antibody protein comprising a domain having an immunoglobulin-like fold and a sequence that is at least 80% identical to the sequence of SEQ ID NO;
81, said non-antibody protein deriving from a reference protein by having a mutated amino acid sequence wherein said non-antibody protein binds with a Kd at least as tight as 1 μ
M to a compound that is not bound as tightly by said reference protein, wherein said contacting is carried out under conditions that allow compound-protein complex formation; and(b) obtaining, from said complex, said derivative protein which binds to said compound.
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27. A method for obtaining a compound which binds to a non-antibody protein, said non-antibody protein comprising a domain having an immunoglobulin-like fold and a sequence that is at least 80% identical to the sequence of SEQ ID NO:
- 81 and deriving from a reference protein by having a mutated amino acid sequence, wherein said non-antibody protein binds with a Kd at least as tight as 1 μ
M to a compound that is not bound as tightly by said reference protein, said method comprising;(a) contacting said derivative protein with a candidate compound, wherein said contacting is carried out under conditions that allow compound-protein complex formation; and (b) obtaining, from said complex, said compound which binds to said derivative proteins.
- 81 and deriving from a reference protein by having a mutated amino acid sequence, wherein said non-antibody protein binds with a Kd at least as tight as 1 μ
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28. A method for detecting a compound in a sample, said method comprising:
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(a) contacting said sample with a non-antibody protein comprising a domain having an immunoglobulin-like fold and a sequence that is at least 80% identical to the SEQ ID NO;
81, said non-antibody protein deriving from a reference protein by having a mutated amino acid sequence wherein said non-antibody protein binds with a Kd at least as tight as 1 μ
M to a compound that is not bound as tightly by said reference protein, wherein said contacting is carried out under conditions that allow compound-protein complex formation; and(b) detecting said complex, thereby detecting said compound in said sample.
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29. A non-antibody protein that binds tumor necrosis factor-α
- (TNF-α
) with a Kd at least as tight as 1 μ
M, said protein having a sequence that is less than 20% identical to TNF-α
receptor and is at least 80% identical to the seciuence of SEQ ID NO;
81. - View Dependent Claims (30, 31, 32)
- (TNF-α
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33. A loop structure on a protein, said loop comprising an amino acid sequences that is at least 80% identical to the sequence of SEQ ID NO:
- 81, wherein said loop binds with a Kd at least as tight as 1 μ
M to a compound that is not bound as tightly by said reference protein.
- 81, wherein said loop binds with a Kd at least as tight as 1 μ
Specification