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Small-molecule mimetics of the β-hairpin flap of HIV-1 protease (HIV-1 PR) were designed based on a 1,4-benzodiazepine scaffold as a strategy to interfere with the flap–flap protein–protein interaction, which functions as a gated mechanism to control access to the active site. Michaelis–Menten kinetics suggested our small-molecules are competitive inhibitors, which indicates the mode of inhibition...
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