Peptide glues the goal of this sbir phase i project is to develop a commercial platform that accelerates and enhances drug discovery efforts for chemically induced proximity (CIP) modalities, and to…

The National Institute of General Medical Sciences awarded Tango Biosciences Inc. $332,917 on April 1, 2026, under SBIR Phase I funding (Assistance Listing 93.859, Biomedical Research and Research Training) to develop a commercial platform accelerating drug discovery for chemically induced proximity modalities using peptide ligands identified through phage display screening.

Tango Biosciences will execute three specific aims over the 12-month period of performance ending March 31, 2027. Aim 1 involves screening 14 phage-displayed combinatorial peptide libraries to discover peptide ligands for BRD4 and CRBN proteins, with synthetic peptides to be validated for binding affinity outside the phage context; the team targets identifying up to 10 different peptide sequences per protein with affinities ranging from 200 nM to 2 mM. Aim 2 requires ligating peptide ligands in various combinations and reformatting them into bispecific modalities that induce binary complexes between BRD4 and CRBN, and between CDK4 and CRBN, using sortase A to link the synthetic peptides and AlphaLISA and mass photometry to assess complex formation. Aim 3 will deliver peptide glues to cells via lipid nanoparticles to demonstrate in vivo proteolysis of the target protein.

Work is performed in Chicago, Illinois. The award is structured as a Project Grant, the standard assistance type for SBIR Phase I research.

Peptide glues the goal of this sbir phase i project is to develop a commercial platform that accelerates and enhances drug discovery efforts for chemically induced proximity (CIP) modalities, and to demonstrate proof of concept using peptide ligands discovered through phage display. Despite significant interest, DIS- covering proximity-inducing molecules, particularly molecular glues, remains a challenging task. Our AP- proach involves screening the world's largest commercially available phage-displayed combinatorial PEP- tide libraries to identify peptides that bind separately to the target protein and E3 ubiquitin ligase and then utilizing them in two novel ways. First, peptides that bind to the target and E3 ligase will be linked together and assessed for their ability, as "peptide glues, to bring the two proteins together in vitro. Second, the glues can be delivered to cells via lipid nanoparticles to demonstrate their ability to induce proteolysis of the target in vivo. The team of scientists at tango biosciences will achieve this goal through the following three specific aims: aim 1. Discover peptide ligands for BRD4 and crbn proteins. Use affinity selection to screen 14 phage-displayed combinatorial peptide libraries to identify peptide ligands for each target. SYN- thetic peptides will be ordered with a biotin tag and confirmed to bind each target outside the context of phage. Milestones include identifying up to 10 different peptide sequences that bind to each protein with affinities ranging from 200 NM to 2 ΜM. Aim 2. Ligate peptide ligands in various combinations to refor- mat them into reagents that induce binary complexes between BRD4 and crbn and CDK4 and crbn. Sortase a will be used to link synthetic peptide ligands into bispecific modalities that will be exam- ined for their ability to induce the formation of binary complexes, as observed by alphalisa and mass PHO- tometry. The small molecule, DBET1, will serve as a positive control for bringing BRD4-crbn together. Milestones include confirming that the peptide ligands for BRD4 and crbn can be configured into peptide glues and establishing sops directly applicable to other CIP systems. Aim 3. Test the efficacy of peptide glues to knock down BRD4 in cells. We will test up to four peptide glues in two human cell lines that EX- press both BRD4 and crbn. Peptide glues will be delivered as lipid nanoparticles, and BRD4 levels will be measured in cell lysates by western blotting. DBET1 will serve as a positive control, and scrambled PEP- tides will serve as negative controls. Milestones include a greater than 70% reduction of cellular BRD4 with at least one peptide glue, but not with its scrambled sequence. Upon completion of this phase i effort, we aim to continue growth in a phase II effort where we apply the peptide glue platform to a diverse range of proximity targets in addition to screening small molecule libraries with displacement assays for small chemicals that bind at the same sites and can serve as starting points to develop molecular glues.