Year: 2023
Type: article
Abstract: The mucosal chemokine CCL28 is a promising target for immunotherapy drug development due to its elevated expression level in epithelial cells and critical role in creating and maintaining an immunosuppressive tumor microenvironment. Using sulfotyrosine as a probe, NMR chemical shift mapping identified a potential receptor-binding hotspot on the human CCL28 surface. CCL28 was screened against 2,678 commercially available chemical fragments by 2D NMR, yielding thirteen verified hits. Computational docking predicted that two fragments could occupy adjoining subsites within the sulfotyrosine recognition cleft. Dual NMR titrations confirmed their ability to bind CCL28 simultaneously, thereby validating an initial fragment pair for linking and merging strategies to design high-potency CCL28 inhibitors.
Source: SLAS DISCOVERY
Institution: Medical College of Wisconsin
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,800
Awards: Evolution of fold-switching in the metamorphic chemokine XCL1, High Performance Digital Console and Sample Jet, Validating CCL28 as a Target for Novel Asthma Therapies using NMR Spectroscopy, Medical Scientist Training Program, Targeting CCL28 as therapy for obstructive lung disease, Structure-based inhibition of chemokine signaling in the inflamed pancreas, Discovering and Exploiting Selectivity within Tandem Bromodomains, Structural Basis for Chemokine Function
OpenAlex ID: W4321602259