1547192-82-4Relevant articles and documents
Small molecule mimetics of an interferon-α receptor interacting domain
Bello, Angelica M.,Wei, Lianhu,Majchrzak-Kita, Beata,Salum, Noruê,Purohit, Meena K.,Fish, Eleanor N.,Kotra, Lakshmi P.
, p. 978 - 985 (2014)
Small molecules that mimic IFN-α epitopes that interact with the cell surface receptor, IFNAR, would be useful therapeutics One such 8-amino acid region in IFN-α2, designated IRRP-1, was used to derive 11 chemical compounds that belong to 5 distinct chemotypes, containing the molecular features represented by the key residues Leu30, Arg33, and Asp35 in IRRP-1 Three of these compounds exhibited potential mimicry to IRRP-1 and, in cell based assays, as predicted, effectively inhibited IFNAR activation by IFN-α Of these, compound 3 did not display cell toxicity and reduced IFN-α- inducible STAT1 phosphorylation and STAT-DNA binding Based on physicochemical properties' analyses, our data suggest that moieties with acidic pKa on the small molecule may be a necessary element for mimicking the carboxyl group of Asp35 in IRRP-1 Our data confirm the relevance of this strategy of molecular mimicry of ligand-receptor interaction domains of protein partners for small molecule drug discovery
