Surface loop structural analogues of fibroblast growth factors

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Hormones – e.g. – prolactin – thymosin – growth factors – etc.

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530350, C07K 1450, C12N 1518

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active

054912202

ABSTRACT:
Structural analogues of fibroblast growth factors have an amino acid sequence replacement in the ninth or tenth .beta.-strand of the factor, or the sequence that corresponds to the surface loop that connects the ninth and tenth .beta.-strands, such that the folding of the molecule is not significantly perturbed. Preferred analogues have the amino acid sequence replacement in the surface loop that extends from the ninth .beta.-strand to the tenth .beta.-strand and have the overall secondary and tertiary structure of the original factor, and bind to heparin and a member or members of the fibroblast growth factor receptor family with high affinity. In some embodiments, the analogues are prepared by replacing the surface loop sequence that connects the ninth and tenth .beta.-strand with another amino acid sequence such as a loop sequence from another structurally related fibroblast growth factor or an interleukin. Preferred analogues exhibit different biological properties and/or receptor binding specificity profiles from native factors.

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