Abstract: An isolated polypeptide, Z domain, derived from B domain of Staphylococcal protein A, comprising a pair of anti-parallel alpha helices that are capable of binding a target, is provided herein. Introduction of an un-natural amino acid in the polypeptide is provided here. Also provided are methods of using the two-helix binders.

Abstract: Provided are in vivo imaging agents comprising muteins of hTLc having detectable binding affinity for c-Met or a domain thereof, coupled to a signal generator, and the mutein coupled to a signal generator is disposed in a pharmaceutically acceptable carrier. Also provided are diagnostic methods using in vivo imaging agents comprising muteins of hTLc having detectable binding affinity for c-Met or a domain thereof.

Abstract: Provided herein are PDGF-R? imaging agents that are polypeptides labeled with a signal generator (e.g., paramagnetic label, a radionuclide, or a fluorophore), wherein the imaging agents bind specifically to PDGFR-?. Also provided are in vivo imaging methods using the imaging agents.

Abstract: Provided herein are methods of reducing liver uptake in vivo of a polypeptide that specifically binds to a target comprising: (a) providing a polypeptide that specifically binds to a target; and (b) substituting at least one basic or at least one neutral amino acid residue of the native polypeptide from step (a) with an acidic amino acid residue to produce a modified polypeptide, wherein the modified polypeptide demonstrates an isoelectric point at least 0.05-0.1 pH points less than the isoelectric point of the native polypeptide. Also provided are polypeptides made using the inventive methods as well as imaging techniques that employ the methods and agents.

Abstract: In an embodiment, a microcode unit for a processor is contemplated. The microcode unit comprises a microcode memory storing a plurality of microcode routines executable by the processor, wherein each microcode routine comprises two or more microcode operations. Coupled to the microcode memory, the sequence control unit is configured to control reading microcode operations from the microcode memory to be issued for execution by the processor. The sequence control unit is configured to stall issuance of microcode operations forming a body of a loop in a first routine of the plurality of microcode routines until a loop counter value that indicates a number of iterations of the loop is received by the sequence control unit.

Abstract: Provided herein are isolated polypeptides derived from the staphylococcal protein A protein B domain comprising a pair of anti-parallel alpha helices that are capable of binding a target. Also provided are nucleic acid sequences encoding such two helix binders, vectors containing the nucleic acid sequences encoding for two helix binders, and host cells transformed with vectors containing the nucleic acid sequences encoding for the two-helix binders. Also provided are methods of using the two helix binders.

Abstract: Provided herein are methods for introducing fluorine atom onto a biomolecule comprising: (i) providing a linker comprising a thiol-reactive terminus and an azido/alkyne-reactive terminus; (ii) reacting the thiol-reactive terminus of the linker with a biomolecule comprising at least one thiol group or a reactive derivative thereof; and (iii) subsequently reacting the azido/alkyne-reactive terminus of the linker with a fluorine-substituted azide or alkyne respectively. Also provided are compositions and method of synthesis of bifunctional linkers and bioconjugates as well as radio-diagnostic agents comprising fluorine-labeled biomolecules.

Abstract: Methods for introducing fluorine atom onto a polypeptide are provided. Also provided are linkers, bioconjugates, and bifunctional compound agents made using the methods, linkers, and bioconjugates. The methods comprise: (i) providing a linker comprising a thiol-reactive terminus and an aldehyde-reactive terminus; (ii) reacting the thiol-reactive terminus of the linker with a polypeptide comprising at least one thiol group or a reactive derivative thereof; and (iii) subsequently reacting the aldehyde-reactive terminus of the linker with a fluorine-substituted aldehyde.

Abstract: This invention relates to multifunctional detection agents useful for providing high-resolution, in vivo imaging of biochemical activity in a living organism. Methods of using these multifunctional detection agents may comprise administering them into a living organism, and then estimating the localization of the detection agent using one modality (i.e., MRI), while concurrently estimating the level of biological activity using a second modality (i.e., optical imaging). One of the multifunctional detection agents comprises a magnetic resonance component and an optical imaging component. The magnetic resonance component comprises a contrast agent that is always activated or “on”. The optical imaging component comprises a plurality of activatable contrast agents or dyes, at least two of which are different from one another, wherein at least one of the activatable contrast agents can be activated or turned “on” only in the presence of a particular event.

Abstract: This invention relates to bifunctional detection agents useful for providing high-resolution, in vivo imaging of biochemical activity in a living organism. Methods of using these bifunctional detection agents may comprise administering them into a living organism, and then estimating the localization of the detection agent using one modality (i.e., MRI), while concurrently estimating the level of biological activity using a second modality (i.e., optical imaging). One of the bifunctional detection agents comprises a magnetic resonance component and an optical imaging component. The magnetic resonance component comprises a contrast agent that is always activated or “on”. The optical imaging component comprises an activatable contrast agent or dye that is activated or turned “on” only in the presence of a particular event.

Abstract: This invention relates to bifunctional detection agents useful for providing high-resolution, in vivo imaging of biochemical activity in a living organism. Methods of using these bifunctional detection agents may comprise administering them into a living organism, and then estimating the localization of the detection agent using one modality (i.e., MRI), while concurrently estimating the level of biological activity using a second modality (i.e., optical imaging). One of the bifunctional detection agents comprises a magnetic resonance component and an optical imaging component. The magnetic resonance component comprises a contrast agent that is always activated or “on”. The optical imaging component comprises an activatable contrast agent or dye that is activated or turned “on” only in the presence of a particular event.