Described herein are methods and systems for identifying protein-protein interactions using particle panels and protein corona formation. Also disclosed herein are systems and methods for enrichment analysis between protein annotations and particle biophysicochemical properties.

The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

Provided herein are methods for identifying pairs of protein binding partners, mutations of which may inform the discovery of pharmaceutically useful small molecules. The methods disclosed herein may allow for the adaptation of the native protein degradation system to modulate specific disease targets at the protein level, in particular, for targets that have long been considered undruggable.

A method to produce novel split-protein sensors are described herein. The method implements a sequence dissimilarity (SD) based design that can identify potential split-sites in proteins to generate a split-protein pair, and then employs structure guided mutagenesis of the fragmented protein interface to generate split-protein sensors. The sensors have a signal to background ratio >200 and can be readily used to monitor protein-protein interactions and their inhibition in cells.

The present disclosure relates to a polypeptide including an Fc-gamma receptor mutant. The Fc-gamma receptor mutant of the present disclosure is optimized by substituting a part of an amino acid sequence of an Fc-gamma receptor with a different amino acid sequence, so as to provide an excellent selective binding ability to immunoglobulins. Therefore, it can be usefully used for increasing in vivo half-life of drugs, detecting and purifying immunoglobulins, inhibiting organ transplant rejections, or preventing or treating autoimmune diseases.

The invention pertains to a heterobifunctional molecule comprising a first and a second binding domain, wherein i) the first binding domain is capable of specific binding to a transmembrane E3 ubiquitin ligase; and ii) the second binding domain is capable of specific binding to a transmembrane protein, wherein simultaneous binding of the heterobifunctional molecule to the transmembrane E3 ubiquitin ligase and the transmembrane protein results in ubiquitination and internalisation of the transmembrane protein. The invention further pertains to the heterobifunctional molecule for use in the treatment of a disease, wherein preferably the disease is at least one of cancer, an auto-immune disease, an inflammatory disease, an infectious disease and a hereditary disease.

Provided herein, inter alia, are stabilizers of protein-protein interactions and methods of identifying and using the same.

The present invention relates to inhibitors of HIF-1 and HIF-2 and uses thereof. The present invention further relates to the inhibitors for use in treatment of diseases. An isolated polypeptide is provided, that prevents dimerization of HIF-1α with HIF-1β and HIF-2α with HIF-1β and/or inhibits the activity of HIF-1 and HIF-2, wherein the polypeptide comprises the amino acid sequence C-X1-X2-X3-Z-X4 (SEQ ID NO: 1) and wherein X1, X2, X3 and X4 are any amino acid and wherein Z is leucine, valine of isoleucine or a non-natural derivative or leucine, valine or isoleucine. The isolated polypeptide prevents dimerization of HIF-1α with HIF-1β and HIF-2α with HIF-1β and inhibits the activity of HIF-1 and HIF-2 by binding to HIF-1α or HIF-1β and/or HIF-2α or HIF-1β.

Photoactive probes and probe systems for detecting biological interactions are described. The photoactive probes include probes that combine both photocleavable and photoreactive moieties. The photoactive probe systems can include a first probe comprising a photocatalytic group and a second probe comprising a group that can act as a substrate for the reaction catalyzed by the photocatalytic group. The probes and probe systems can also include groups that can specifically bind to a binding partner on a biological entity of interest and a detectable group or a precursor thereof. The probes and probe systems can detect spatiotemporal interactions of proteins or cells. In some embodiments, the interactions can be detected in live cells. Also described are methods of detecting the biological interactions.