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Novel PTP1B inhibitors identified by DNA display of fragment pairs

Ioannidou, Heraklidia A.
Ciobanu, Mihai
Morieux, Pierre
Published in Bioorganic & Medicinal Chemistry Letters. 2016, vol. 26, no. 3, p. 1080-1085
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 libraryPeptide nucleic acid (PNA)Fragment based drug discoveryPTP1B
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Research group Groupe Winssinger
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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 https://archive-ouverte.unige.ch/unige:80097

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Deposited on : 2016-01-27

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