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Scientific article
English

Novel PTP1B inhibitors identified by DNA display of fragment pairs

Published inBioorganic & medicinal chemistry letters, vol. 26, no. 3, p. 1080-1085
Publication date2016
Abstract

DNA display of PNA-encoded libraries was used to pair fragments containing different phosphotyrosine surrogates with diverse triazoles. Microarray-based screening of the combinatorially paired fragment sets (62,500 combinations) against a prototypical phosphatase, PTP1B, was used to identify the fittest fragments. A focused library (10,000 members) covalently pairing identified fragments with linkers of different length and geometry was synthesized. Screening of the focused library against PTP1B and closely related TCPTP revealed orthogonal inhibitors. The selectivity of the identified inhibitors for PTP1B versus TCPT was confirmed by enzymatic inhibition assay.

Keywords
  • DNA-encoded library
  • Peptide nucleic acid (PNA)
  • Fragment based drug discovery
  • PTP1B
Research group
Citation (ISO format)
BARLUENGA BADIOLA, Sofia et al. Novel PTP1B inhibitors identified by DNA display of fragment pairs. In: Bioorganic & medicinal chemistry letters, 2016, vol. 26, n° 3, p. 1080–1085. doi: 10.1016/j.bmcl.2015.11.102
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Article (Published version)
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Identifiers
ISSN of the journal0960-894X
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Technical informations

Creation01/26/2016 2:01:00 PM
First validation01/26/2016 2:01:00 PM
Update time03/15/2023 12:06:26 AM
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