Biphenyl hydrolase-like protein (BPHL)

Biphenyl hydrolase-like protein (BPHL) is a serine hydrolase enzyme found in humans, originally cloned from breast carcinoma tissue, and predominantly expressed in the liver and kidney[1][3]. It is best known for catalyzing the hydrolytic activation of certain amino acid ester prodrugs, such as the antiviral agents valacyclovir and valganciclovir, converting them into their active forms, acyclovir and ganciclovir, respectively[1][2][3]. BPHL shows a preference for hydrophobic amino acid promoieties and contains a classic catalytic triad (Ser-His-Asp) within a hydrophobic binding pocket[2][3]. In addition to its role in drug bioactivation, BPHL is highly efficient at hydrolyzing homocysteine thiolactone, suggesting a role in detoxification and the prevention of protein homocysteinylation[1]. While crucial for some prodrug strategies, BPHL is not strictly required for all metabolism of valacyclovir, as compensatory enzymes can take over in its absence; however, its selectivity and catalytic properties make it a frequent molecular target for oral delivery optimization of nucleoside-based therapeutics[3].

Other names

Serine hydrolase BPHLMCNAABph-rpVACVaseValacycloviraseBiphenyl hydrolase-related proteinBreast epithelial mucin-associated antigenL-homocysteine-thiolactonase BPHLValacyclovir hydrolaseBPH-RP

Hydrolytic activation of amino acid ester prodrugs (BPHL cleaves valine ester to active nucleoside drugs)