MUTANTS OF IGF BINDING PROTEINS AND METHODS OF PRODUCTION OF ANTAGONISTS THEREOF

摘要

The present invention provides a crystal suitable for X-ray diffraction, comprising a complex of insulin-like growth factor I or II (IGF) and a polypeptide consisting of the amino acids 39-91 of IGFBP-1, the amino acids 55-107 of IGFBP-2, the amino acids 47-99 of IGFBP-3, the amino acids 39-91 of IGFBP-4, the amino acids 40-92 of IGFBP-5, or the amino acids 40-92 of IGFBP-6 or a fragment thereof consisting at least of the 9 to 12 cysteine of IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, or IGFBP-5 or at least of the 7 to 10 cysteine of IGFBP-6; methods for the determination of the atomic coordinates of such a crystal; IGFBP mutants with enhanced binding affinity for IGF-I and/or IGF-II, and methods to identify and optimize small molecules which displace IGFs from their binding proteins.