Design, synthesis and validation of a new Crimped Head-Piece for DNA-Encoded libraries generation.

Autor: Rama-Garda R; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain; BioFarma, Universidad de Santiago de Compostela (USC), Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), A Coruña 15782, Spain. Electronic address: rama_ramon@lilly.com., Martin-Ortega MD; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain., Sánchez AJ; LGC Biosearch Technologies, Petaluma, CA, USA., Priego J; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain., de Blas J; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain., Torrado A; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain., Domínguez E; Genomic Medicine, Universidad de Santiago de Compostela (USC), Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), A Coruña, Spain., Haro R; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain., Rivera-Sagredo A; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain., Román JP; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain., Lorite MJ; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain., Johansson HE; LGC Biosearch Technologies, Petaluma, CA, USA., Loza MI; BioFarma, Universidad de Santiago de Compostela (USC), Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), A Coruña 15782, Spain., Amigo J; Fundación Pública Galega de Medicina Xenómica (FPGMX), Servizo Galego de Saúde (SERGAS), Instituto de Investigaciones Sanitarias (IDIS), A Coruña 15706, Spain., Sobrino B; Fundación Pública Galega de Medicina Xenómica (FPGMX), Servizo Galego de Saúde (SERGAS), Instituto de Investigaciones Sanitarias (IDIS), A Coruña 15706, Spain., Lallena MJ; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain., Toledo MÁ; Discovery Chemistry Research & Technologies, Lilly Research Laboratories, Eli Lilly and Company, Alcobendas, Madrid 28108, Spain.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2024 Feb 01; Vol. 99, pp. 117596. Date of Electronic Publication: 2024 Jan 11.
DOI: 10.1016/j.bmc.2024.117596
Abstrakt: Codification of DNA Encoded Libraries (DELs) is critical for successful ligand identification of molecules that bind a protein of interest (POI). There are different encoding strategies that permit, for instance, the customization of a DEL for testing single or dual pharmacophores (single strand DNA) or for producing and screening large diversity libraries of small molecules (double strand DNA). Both approaches challenges, either from the synthetic and encoding point of view, or from the selection methodology to be utilized for the screening. The Head-Piece contains the DNA sequence that is attached to a chemical compound, allowing the encoding of each molecule with a unique DNA tag. Designing the Head-Piece for a DNA-encoded library involves careful consideration of several key aspects including DNA barcode identity, sequence length and attachment chemistry. Here we describe a double stranded DNA versatile Head-Piece that can be used for the generation of single or dual pharmacophore libraries, but also shows other advanced DEL functionalities, stability and enlarged encoding capacity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: