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Phenylalanine‐Based DNA‐Encoded Chemical Libraries for the Discovery of Potent and Selective Small Organic Ligands Against Markers of Cancer and Immune Cells
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Phenylalanine‐Based DNA‐Encoded Chemical Libraries for the Discovery of Potent and Selective Small Organic Ligands Against Markers of Cancer and Immune Cells
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Phenylalanine‐Based DNA‐Encoded Chemical Libraries for the Discovery of Potent and Selective Small Organic Ligands Against Markers of Cancer and Immune Cells
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Journal Article
Phenylalanine‐Based DNA‐Encoded Chemical Libraries for the Discovery of Potent and Selective Small Organic Ligands Against Markers of Cancer and Immune Cells
2025
Overview
DNA‐encoded chemical libraries (DELs) are powerful tools for drug discovery, enabling the high‐throughput screening of vast libraries of small molecules against target proteins of pharmaceutical interest. Here, the synthesis of two new DELs, named FM‐DEL1 and FM‐DEL2, including 7′710 and 5′697’690 compounds, respectively is described. These libraries are constructed by installing one or two sets of building blocks on a phenylalanine central scaffold. FM‐DELs are screened against markers of prostate cancer, and renal cell carcinoma, and against an immunological target expressed on the surface of natural killer cells. Highly potent and selective binders with affinity constants in the nanomolar range are obtained from DEL screenings against those targets. Small‐molecule ligands against tumor‐associated antigens are used to develop small‐molecule radiopharmaceuticals that selectively accumulate at cancer sites after systemic administration. FM‐DEL1 and FM‐DEL2 are constructed by installing one or two sets of building blocks on a phenylalanine central scaffold. FM‐DELs are screened against markers of prostate, and renal cell carcinoma, and against an immunological target expressed on the surface of natural killer cells. Highly potent and selective binders with affinity constants in the nanomolar range are isolated for those targets.
Publisher
John Wiley & Sons, Inc,Wiley
Subject
/ Antigens
/ Biomarkers, Tumor - metabolism
/ Codes
/ DNA‐encoded chemical library
/ Humans
/ Ligands
/ Prostatic Neoplasms - drug therapy
/ Prostatic Neoplasms - immunology
/ Proteins
/ Small Molecule Libraries - chemistry
/ Small Molecule Libraries - pharmacology
/ small molecule radiopharmaceuticals
/ Tumors
