{"doi":"10.17615/nspe-2n88","title":"Discovery and Characterization of Peptide Inhibitors for Calcium and Integrin Binding Protein 1","abstract":"Calcium and integrin binding protein 1 (CIB1) is an EF-hand-containing, small intracellular protein that has recently been implicated in cancer cell survival and proliferation. In particular, CIB1 depletion significantly impairs tumor growth in triple-negative breast cancer (TNBC). Thus, CIB1 is a potentially attractive target for cancer chemotherapy that has yet to be validated by a chemical probe. To produce a probe molecule to the CIB1 helix 10 (H10) pocket and demonstrate that it is a viable target for molecular intervention, we employed random peptide phage display to screen and select CIB1-binding peptides. The top peptide sequence selected, UNC10245092, was produced synthetically, and binding to CIB1 was confirmed by isothermal titration calorimetry (ITC) and a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. Both assays showed that the peptide bound to CIB1 with low nanomolar affinity. CIB1 was cocrystallized with UNC10245092, and the 2.1 Å resolution structure revealed that the peptide binds as an α-helix in the H10 pocket, displacing the CIB1 C-terminal H10 helix and causing conformational changes in H7 and H8. UNC10245092 was further derivatized with a C-terminal Tat-derived cell penetrating peptide (CPP) to demonstrate its effects on TNBC cells in culture, which are consistent with results of CIB1 depletion. These studies provide a first-in-class chemical tool for CIB1 inhibition in cell culture and validate the CIB1 H10 pocket for future probe and drug discovery efforts.","journal":"INDIGO (University of Illinois at Chicago)","year":2022,"id":310238,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1006088,"name":"J.W. Bogart","orcid":null,"position":1,"is_corresponding":false},{"id":1006134,"name":"S.H. Cholensky","orcid":null,"position":2,"is_corresponding":false},{"id":1006074,"name":"V.A. Haberman","orcid":null,"position":3,"is_corresponding":false},{"id":1006135,"name":"K.H. Pearce","orcid":null,"position":4,"is_corresponding":false},{"id":1006136,"name":"A.S. Godoy","orcid":null,"position":5,"is_corresponding":false},{"id":541510,"name":"S.V. Frye","orcid":null,"position":6,"is_corresponding":false},{"id":1006137,"name":"T.M. Leisner","orcid":null,"position":7,"is_corresponding":false},{"id":835734,"name":"L.V. Parise","orcid":null,"position":8,"is_corresponding":false},{"id":1006138,"name":"J.E. Larson","orcid":null,"position":9,"is_corresponding":false},{"id":1006139,"name":"A.C. Puhl","orcid":null,"position":10,"is_corresponding":false},{"id":1006140,"name":"J.L. Norris-Drouin","orcid":null,"position":11,"is_corresponding":false},{"id":978010,"name":"A.A. Bowers","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:33:19.712967Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}