Profiling cells with DELs: Small molecule fingerprinting of cell surfaces

Jason Deng; Svetlana Belyanskaya; Ninad Prabhu; Christopher Arico-Muendel; Hongfeng Deng; Christopher B. Phelps; David I. Israel; Hongfang Yang; Joseph Boyer; G. Joseph Franklin; Jeremy L. Yap; Kenneth E. Lind; Ching-Hsuan Tsai; Christine Donahue; Jennifer D. Summerfield

SLAS Discovery (Jul 2024)

Profiling cells with DELs: Small molecule fingerprinting of cell surfaces

Jason Deng,
Svetlana Belyanskaya,
Ninad Prabhu,
Christopher Arico-Muendel,
Hongfeng Deng,
Christopher B. Phelps,
David I. Israel,
Hongfang Yang,
Joseph Boyer,
G. Joseph Franklin,
Jeremy L. Yap,
Kenneth E. Lind,
Ching-Hsuan Tsai,
Christine Donahue,
Jennifer D. Summerfield

Affiliations

Jason Deng: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Svetlana Belyanskaya: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Ninad Prabhu: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Christopher Arico-Muendel: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Hongfeng Deng: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Christopher B. Phelps: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
David I. Israel: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Hongfang Yang: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Joseph Boyer: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
G. Joseph Franklin: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Jeremy L. Yap: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Kenneth E. Lind: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Ching-Hsuan Tsai: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Christine Donahue: GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA
Jennifer D. Summerfield: Corresponding author at: GSK, 200 Cambridgepark Drive, Cambridge, MA 02140.; GSK Molecular Modalities Discovery, 200 Cambridgepark Drive, Cambridge, MA, 02140, USA

Journal volume & issue: Vol. 29, no. 5
p. 100171

Abstract

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DNA-encoded small molecule library technology has recently emerged as a new paradigm for identifying ligands against drug targets. To date, it has been used to identify ligands against targets that are soluble or overexpressed on cell surfaces. Here, we report applying cell-based selection methods to profile surfaces of mouse C2C12 myoblasts and myotube cells in an unbiased, target agnostic manner. A panel of on-DNA compounds were identified and confirmed for cell binding selectivity. We optimized the cell selection protocol and employed a novel data analysis method to identify cell selective ligands against a panel of human B and T lymphocytes. We discuss the generality of using this workflow for DNA encoded small molecule library selection and data analysis against different cell types, and the feasibility of applying this method to profile cell surfaces for biomarker and target identification.

Published in SLAS Discovery

ISSN: 2472-5552 (Print); 2472-5560 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General); Technology: Chemical technology: Biotechnology
Website: https://www.journals.elsevier.com/slas-discovery

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Abstract

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