摘要:
The NK1 fragment of hepatocyte growth factor (HGF) binds to and activates the Met receptor, a transmembrane receptor tyrosine kinase that plays a critical role in embryonic development and organ formation. The instant application discloses NK1 variant polypeptides which act as agonists or antagonists of HGF. Further disclosed are covalently linked NK1 variant polypeptides. Many of the disclosed variant polypeptides possess improved stability characteristics.
摘要:
Interpenetrating network hydrogels are described that may be incorporated into wound dressings and/or in implants. The properties of the interpenetrating network hydrogel may be tuned to control an amount of moisture in a wound environment. The devices, methods, and kits described herein may be adapted to treat a variety of wound types at a variety of healing stages over a range of time scales. Some hydrogels may be configured to deliver one or more vulnerary agents to a wound. The interpenetrating network hydrogels may also be adapted to control a rate and/or amount of moisture uptake so that the hydrogels may be used as expandable implants to expand tissue.
摘要:
Compositions that are EGF polypeptides that possess improved biological activity as compared to the biological activity exhibited by wild-type EGF are provided. Also provided are methods for the preparation of these mutants, methods for the use of these mutants, methods for rationally designing new polypeptide mutants, and methods for screening mutants polypeptides to identify novel EGF mutants with desirable biological activities.
摘要:
The present invention is based, in part, on our discovery that EGF can be engineered to generate mutants that bind to the EGF receptor (EGFR) of a cell and that have a desirable effect on the activity of the cell. For example, the mutants can agonize the receptor (i.e., increase a biological activity of the receptor), or antagonize the receptor (i.e., decrease or inhibit a biological activity of the receptor). In turn, the rate at which the cell proliferates, for example, can be changed. Moreover, some of these mutants bind EGFR with a higher affinity than wild-type EGF exhibits. The affinity may increase by about, for example, 2-, 5-, 10-, 15-, 20-, 25-, 30-, 50-, or 100-fold relative to wild-type EGF.
摘要:
Polypeptides comprising variant vascular endothelial growth factor sequences are provided. The polypeptides are useful in cancer imaging, cancer diagnosis, monitoring and treatment as well as treatment of diseases characterized by excessive neovascularization.
摘要:
Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL and its ligand GAS6.
摘要:
Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against αIIbβ3 integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to αIIbβ3 integrin or to both αIIbβ3 and αVβ3 integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for αIIbβ3 integrin.
摘要:
Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL and its ligand GAS6.
摘要:
Surface modification methods for an interpenetrating polymer network (IPN) hydrogel to provide a basis for cell or tissue attachment are provided. The method involves the activation of functional groups on the surface of the IPN hydrogel. The activated functional groups are then reacted with amine-containing molecules or hydroxyl-containing molecules. The methods (i) can be performed in an aqueous environment and do not require the use of any organic solvent, (ii) do not require UV treatment, thereby avoiding denaturation of the IPN hydrogel or proteins, and/or (iii) can be performed as a one pot reaction.
摘要:
Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against αIIbβ3 integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to αIIbβ3 integrin or to both αIIbβ3 and αVβ3 integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for αIIbβ3 integrin.