Biphenyl hydrolase-like protein (BPHL) (BPHL)

Biphenyl hydrolase-like protein (BPHL), commonly referred to as valacyclovirase, is a serine hydrolase that plays a pivotal role in the metabolic activation of antiviral prodrugs. It is primarily responsible for the rapid hydrolysis of L-valyl esters, specifically converting valacyclovir into acyclovir and valganciclovir into ganciclovir (Kim et al., 2003; UniProt Q86WA1). The enzyme is highly expressed in the liver and small intestine, which facilitates the high oral bioavailability of these nucleoside analogs compared to their parent compounds (Lai et al., 2008). BPHL belongs to the alpha/beta-hydrolase fold family and is unique for its substrate specificity toward alpha-amino acid esters (Puey et al., 1993). While its endogenous physiological function is not entirely characterized, its efficiency in prodrug conversion makes it a critical factor in the treatment of herpesvirus and cytomegalovirus infections (Zhu et al., 2000). Understanding the activity and expression of BPHL is essential for predicting the pharmacokinetic profile and therapeutic efficacy of valyl ester-based medications.

Other names

ValacycloviraseVACVaseBiphenyl hydrolase-likeBPH-like proteinalpha-amino acid ester hydrolase

Enzymatic hydrolysis of the L-valyl ester bond of prodrugs to release active antiviral nucleoside analogs.