Abstract: In aspects, the invention provides a polypeptide construct comprising (a) a first polypeptide comprising an amino acid sequence derived from a basic helix of a transcription factor protein that comprises a basic helix-loop-helix domain; and (b) a second polypeptide comprising an amino acid sequence derived from a helix that extends in the C-terminal direction from the end of the loop of a basic helix-loop-helix domain of a transcription factor protein that comprises a basic helix-loop-helix domain; wherein the first polypeptide and the second polypeptide are linked through an interpolypeptide covalent linkage. Additional aspects of the invention are as described herein.

Abstract: 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.

Abstract: The invention relates to bifunctional stapled or stitched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stitched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stitched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stitched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Uses of the inventive bifunctional stapled or stitched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.

Abstract: The present disclosure provides macrocyclic and macrobicyclic peptides with secondary structures that are stabilized over the corresponding non-cyclic peptides. The macrocyclic and macrobicyclic peptides are formed from peptides with adduct-forming, complementary reactive side chain moieties.

Abstract: Radioisotope-labeled small molecule activity-based probes that target the cancer associated serine hydrolase neutral cholesterol ester hydrolase 1 (NCEH1) are described. The probes can undergo a reaction with the NCEH1, resulting in covalent bonding of a portion of the probe molecule to the NCEH1. Also described are methods of labeling NCEH1 in biological samples, such as cells or tissue, and methods of visualizing tumors using the radioisotope-labeled NCEH1 probes as tracer compounds, either alone or in combination with assessing the efficacy of a cancer treatment or potential cancer treatment.

Abstract: Aspects of the disclosure relate to a method for evaluating two or more target proteins of interest from the same family in a specified functional form, the method comprising: (i) contacting a composition comprising or suspected of comprising the two or more proteins of interest with a molecular construct comprising: a targeting group operatively linked to a retrieval tag; wherein the targeting group specifically binds to the specialized functional form of the two or more target proteins of interest; (ii) contacting the composition with at least two antibody-oligo constructs, wherein at least one of the constructs comprises a first antibody operatively linked to a first oligo and at least a second construct comprises a second antibody operatively linked to a second oligo; wherein the first antibody specifically binds to one of the two or more target proteins of interest and the second antibody specifically binds to the other of the two or more target proteins of interest; (iii) contacting the composition with

Abstract: The present invention relates to peptides and protein mimetics and their therapeutic and research use. In particular, the present invention provides synthetic, stabilized DNA binding domain peptides and methods of using such peptides as therapeutic agents.

Abstract: The invention relates to bifunctional stapled or stiched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stiched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stiched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stiched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Usesses of the inventive bifunctional stapled or stiched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.

Abstract: The present invention provides inventive polypeptides comprising a C terminal RAB binding domain (RabBD) of RAB family interacting proteins (FIPs) stabilized by peptide stapling, and pharmaceutical compositions thereof. Also provided are methods for modulating RAB function comprising contacting an inventive stapled polypeptide with a RAB protein, and methods of treatment associated with modulation of RAB activity. The present invention also provides methods of making the inventive stapled polypeptides by ring closing metathesis of unstapled polypeptide precursors.

Abstract: The invention relates to bifunctional stapled or stiched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stiched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stiched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stiched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Usesses of the inventive bifunctional stapled or stiched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.

Abstract: The invention relates to bifunctional stapled or stitched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stitched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stitched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stitched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Uses of the inventive bifunctional stapled or stitched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.

Abstract: The present invention provides inventive polypeptides comprising a C terminal RAB binding domain (RabBD) of RAB family interacting proteins (FIPs) stabilized by peptide stapling, and pharmaceutical compositions thereof. Also provided are methods for modulating RAB function comprising contacting an inventive stapled polypeptide with a RAB protein, and methods of treatment associated with modulation of RAB activity. The present invention also provides methods of making the inventive stapled polypeptides by ring closing metathesis of unstapled polypeptide precursors.

Abstract: Serine hydrolases are implicated in malconditions such as cancer, central nervous system disorders, cardiovascular disorders, obesity, and metabolic disorders. Many serine hydrolases expressed in proteomic libraries are of unknown function in vivo. Compounds identified through library versus library screening can be used for treatment of malconditions associated with the specific serine hydrolase KIAA1363 (also known as AADACL1). A library of inhibitors of KIAA1363 was prepared and candidate compounds were identified as a potent inhibitors having submicromolar IC50 values. An exemplary compound of the invention was shown to be an effective inhibitor of prostate cancer pathogenesis. Other inhibitory compounds of the invention comprising fluorophore groups are shown to be effective in spatial and temporal localization of the serine hydrolase in cells and tissues.

Abstract: The invention relates to bifunctional stapled or stiched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stiched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stiched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stiched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Uses of the inventive bifunctional stapled or stiched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.