Florida State University Research Foundation, Inc.

Mayo Foundation for Medical Education and Research

Michael Blaber

Vikash Kumar Dubey

Jihun Lee

Liam M Longo

Sachiko I Blaber

Moses Rodriguez

Isobel A Scarisbrick

Stephen R Brych

Xue Xia

A method of making a synthetic foldable having a tertiary structure emulating the tertiary structure of a reference foldable protein is described. The method includes determining a folding nucleus peptide sequence associated with folding the reference foldable protein. The synthetic foldable protein is synthesized by including the determined folding nucleus peptide sequence and at least one repeat thereof in the peptide sequence of the synthetic foldable protein.

Synthetic foldable proteins generated from peptide segments of folding nuclei of reference proteins

Mutant fibroblast growth factor (FGF) proteins having a polypeptide sequence with a high sequence identity to proteins encoded by members of the Fgf-1 subfamily of genes from a mammalian species, such as human, and with a specific amino acid substitution of an alanine at a position corresponding to amino acid position 66 of human FGF-1 with a cysteine and/or a specific amino acid substitution of a phenylalanine at a position corresponding to amino acid position 132 of human FGF-1 with a tryptophan (based on the 140 amino acid numbering scheme of human FGF-1) are provided. Other amino acid mutations or substitutions may be combined. Polynucleotide sequences encoding the mutant FGF proteins and host cells containing such polynucleotide sequences are provided. Methods of administering a mutant FGF protein to an individual to treat an ischemic condition or disease or a wound or tissue injury are also provided.

Fibroblast growth factor mutants having improved functional half-life and methods of their use

The present invention relates to a top-down symmetric deconstruction approach which provides a novel alternative means to successfully identify a useful polypeptide 'building block' for subsequent 'bottom-up' de novo design of target protein architecture. The present invention also pertains to a novel peptides isolated by top-down symmetric deconstruction which may be useful for design or directed evolution of novel proteins with novel functionalities.

Method for development of a peptide building block useful for de novo protein design

An animal restraining harness or jacket and a method of use thereof, for protecting the shoulder and upper abdomen when experimental/surgical procedures are performed and when the experimental/surgical sites must be protected from biting, scratching, and other unwanted contact. The jacket generally includes a shoulder region and collar extensions, where the shoulder region is connected to the collar extensions. The collar extensions are wrapped and secured around the collar or neck area of the animal, and the shoulder region is wrapped and secured around the shoulder and torso area of the animal. Preferably, the collar extensions and shoulder region are secured on the dorsal side of the animal, thus providing a dorsal gap therebetween. This harnesses the animal effectively and prevents escape from the restraining jacket.

Small animal restraining harness or jacket

Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residue 12 is substituted with threonine and/or residue 134 is substituted cysteine, valine or threonine to render the polypeptide more stable and/or to increase its mitogenecity.

Mutants of human fibroblast growth factor having increased stability and/or mitogenic potency

Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residue 12 is substituted with cysteine and/or residue 134 is substituted cysteine, valine or threonine to render the polypeptide more stable and/or to increase its mitogenecity.

Mutants of human FGF-1 are disclosed having increased stability and mitogenic potency. In the FGF-1 polypeptide, primarily residue 12 is substituted with valine and residue 134 is substituted cysteine or threonine to render the polypeptide more stable and/or to increase its mitogenecity.

An engineered, purified polypeptide of acidic fibroblast growth factor (FGF-1) is described, the amino acid sequence of which consists essentially of SEQ ID NO: 1. The engineered polypeptide provides 70 times the mitogenic activity of wild type acidic fibroblast growth factor. Other engineered FGFs are also described, having altered properties, including reduced heparin binding affinity and increased mitogenicity as demonstrated with a model mammalian cell line derived from mice, NIH 3T3 fibroblasts.

Engineered human acidic fibroblast growth factors and associated methods

The &#x3b2;-trefoil protein human fibroblast growth factor-1 (FGF-1) is made up of a six-stranded anti-parallel &#x3b2;-barrel closed off on one end by three &#x3b2;-hairpins, thus exhibiting a three-fold axis of structural symmetry. The N- and C-termini &#x3b2;-strands hydrogen bond to each other and are postulated from both NMR and X-ray structure data to represent a structurally-weakened region of the &#x3b2;-barrel. Val mutations within the N- and C-termini &#x3b2;-strands are shown to stabilize the structure and to increase van der Waals contacts by filling local cavities present within this region. Mutations that increase van der Waals contacts between both the N- and C-termini &#x3b2;-strands are generally associated with significant reductions in the unfolding kinetics, and also increase the cooperativity of unfolding. Surprisingly, several mutant polypeptides herein disclosed greatly exceed the wild-type polypeptide in ability to stimulate human fibroblasts to proliferate.

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Tallahassee, FL, United States of America

Michael Blaber