Enhancing Drug-Target Interactions: Benzophenone Photo-Reactivity and Click Chemistry Modifications

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The benzophenone group functions similarly to the diazirine group, as when exposed to UV irradiation, it forms covalent bonds with target proteins. This facilitates the attachment of drugs to their biological targets, enabling the identification of drug-binding interactions and the precise mapping of binding sites.

By utilising click chemistry, an alkyne moiety (green) was incorporated at various positions on the terminal benzyl group, specifically at the para (B) and meta (C) positions. Meta-substitution (C) demonstrated enhanced efficacy, as it effectively lowers the HOMO-LUMO energy gap through enhanced conjugation, thereby increasing the probe’s electrophilicity and improving its interactions with biological targets. The reduction in the energy gap facilitates electron excitation, enhancing the photo reactivity of the benzophenone probe. Additionally, the presence of the alkyne contributes to increased structural rigidity, which helps maintain an optimal binding conformation and improves the probe’s overall stability toward biological targets.