Methods and biomarker panels for detecting and treating pancreatic disease, including pancreatic cancer, are provided in association with determining and inhibiting expression levels of certain GPCRs, including GPR68, in particular in pancreatic cancer associated fibroblasts.

A method for screening compounds for their ability to interact with transmembrane proteins is provided. Also provided is a method for determining whether proteins such as transmembrane proteins are able to oligomerise.

The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.

The present disclosure provides compositions comprising an opsin polypeptide and an arrestin polypeptide and their use thereof. Exemplary embodiments provide a composition including an opsin polypeptide, or an opsin polypeptide and an arrestin polypeptide, wherein at least one of the opsin or arrestin polypeptide comprises at least one mutation that increases a temporal resolution of the opsin polypeptide’s response to light. The opsin polypeptide and the arrestin polypeptide can be operably linked or separate. Additionally, use of said compositions for restoring retinal photosensitivity or treating a retinal degenerative condition is also provided.

Bioluminescence resonance energy transfer (BRET) biosensors for assessing the intracellular localization, internalization and trafficking into cellular compartments of proteins such as receptors, and other biomolecules such as second messengers, are disclosed. These biosensors, which are dependent on the concentration/density of the BRET donor and acceptor in cellular compartments rather that specific protein-protein interactions, use a Renilla GFP/Luc BRET pair, which allows the robust and reproducible monitoring of protein trafficking/localization, with a sensitivity compatible with high-throughput screening (HTS). The use of these biosensors for various applications, including assessing/monitoring protein endocytosis, recycling and intra-cellular trafficking, receptor maturation/rescue by pharmacological chaperones, various endocytosis/exocytosis processes, activation/inhibition, as well as biomolecule concentration/density in different cellular compartments, is also disclosed.

The present invention refers to a GPR101 inhibitor, antagonist or inverse agonist or inverse agonist for use in preventive and/or therapeutic treatment of diseases selected from the group consisting of acromegaly and gigantism and to methods for preventive and/or therapeutic treatment of diseases selected from the group consisting of acromegaly and gigantism wherein to a subject GPR101 inhibitor, antagonist or inverse agonist is administered. Further, the present invention provides a GPR101 agonist for use in preventive and/or therapeutic treatment of disorders selected from the group consisting of dwarfism, short stature, hypopituitarism and a disease of low levels of pituitary hormone secretion and to methods for preventive and/or therapeutic treatment of diseases selected from the group consisting of dwarfism, short stature, hypopituitarism and a disease of low levels of pituitary hormone secretion wherein to a subject GPR101 agonist is administered. The present invention also provides GHRH inhibitors, antagonists or inverse agonists and GH antagonists for use in the therapeutic treatment of X-linked acrogigantism (X-LAG syndrome). In addition, the present invention refers to a method of increasing body mass and/or body size of livestock comprising administering to livestock an effective amount of GPR101 agonist. Further, the present invention is directed to a non-human transgenic animal, comprising as expressed transgene a gene encoding GPR101 or overexpressing endogenous GPR101 gene.

Newly identified mammalian taste-cell-specific G protein-coupled receptors, and the genes and cDNA encoding said receptors are described. Specifically, T1R G protein-coupled receptors active in taste signaling, and the genes and cDNA encoding the same, are described, along with methods for isolating such genes and for isolating and expressing such receptors. Methods for representing taste perception of a particular taste stimulus in a mammal are also described, as are methods for generating novel molecules or combinations of molecules that elicit a predetermined taste perception in a mammal, and methods for simulating one or more tastes. Further, methods for stimulating or blocking taste perception in a mammal are also disclosed.

A mechanism is provided for utilizing a nanodevice to distinguish molecules with different structure. The molecules translocate through or across a nanochannel filled with a electrolyte solution. An electrical signal through the nanochannel is measured for every translocation event. Inner surfaces of the nanochannel include a functional layer, which is a coating to functionalize the nanochannel, in which the functional layer is configured to interact with predetermined ones of the molecules during translocation events. It is determined that a combination of at least two different molecules is formed based on predetermined ones of the molecules interacting with the functional layer to change the electrical signal and/or change a translocation time for the translocation event.

Ghrelin is a peptide hormone that binds its receptor, growth hormone secretatgogue receptor 1a (GHS-R1 a, ghrelin receptor), to promote adiposity and obesity in mammals. Ghrelin and its receptor are targets for therapeutic intervention to treat obesity-related disease and cancer. A soluble decoy GHS-R1 a receptor is developed that binds ghrelin in the periphery, preventing ghrelin from binding GHS-R1 on cells, thereby antagonizing ghrelin to treat obesity-related pathological conditions and cancer. GHS-R1 a is a transmembrane protein comprising an N-terminal extracellular domain (Nt), seven transmembrane regions and three extracellular loops (EC1, EC2 and EC3). The Nt, EC1 and EC2 are linked together, in the absence of the transmembrane regions, and fused to a Fc from an immunoglobulin, to create the decoy GHS-R1 a fusion protein, GHSR-Fc. The GHSR-Fc inhibits adiposity and weight gain in mice on a high fat diet (HFD), while the Nt and ECs on their own have no significant effect.

The present invention describes the novel molecular entities, nanodisc clathrates, the method of preparation, and the use of these molecular entities for solution phase analysis or crystallization.