ArticleMolecular pharmaceutics2010
Specificity of a prodrug-activating enzyme hVACVase: the leaving group effect.
Article in Molecular pharmaceutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Breast Cancer: Challenges in the Treatment and Prodrug Strategies.Mini reviews in medicinal chemistry · 2026Review
- Prodrug Therapies for Infectious and Neurodegenerative Diseases.Pharmaceutics · 2022Review
- Prodrugs for Improved Drug Delivery: Lessons Learned from Recently Developed and Marketed Products.Pharmaceutics · 2020Review
- Computational Simulations to Guide Enzyme-Mediated Prodrug Activation.International journal of molecular sciences · 2020Review
- Computational modeling and in-vitro/in-silico correlation of phospholipid-based prodrugs for targeted drug delivery in inflammatory bowel disease.Journal of computer-aided molecular design · 2017Article
- Enzymatic activation of double-targeted 5'-O-L-valyl-decitabine prodrug by biphenyl hydrolase-like protein and its molecular design basis.Drug delivery and translational research · 2017Article
- Synthesis and characterization of valyloxy methoxy luciferin for the detection of valacyclovirase and peptide transporter.Bioorganic & medicinal chemistry letters · 2014Article
- Modern prodrug design for targeted oral drug delivery.Molecules (Basel, Switzerland) · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Human valacyclovirase (hVACVase) is a prodrug-activating enzyme for amino acid prodrugs including the antiviral drugs valacyclovir and valganciclovir. In hVACVase-catalyzed reactions, the leaving group of the substrate corresponds to the drug moiety of the prodrug, making the leaving group effect essential for the rational design of new prodrugs targeting hVACVase activation. In this study, a series of valine esters, phenylalanine esters, and a valine amide were characterized for the effect of the leaving group on the efficiency of hVACVase-mediated prodrug activation. Except for phenylalanine methyl and ethyl esters, all of the ester substrates exhibited a relatively high specificity constant (k(cat)/K(m)), ranging from 850 to 9490 mM(-1)·s(-1). The valine amide Val-3-APG exhibited significantly higher K(m) and lower k(cat) values compared to the corresponding ester Val-3-HPG, indicating poor specificity for hVACVase. In conclusion, the substrate leaving group has been shown to affect both binding and specific activity of hVACVase-catalyzed activation. It is proposed that hVACVase is an ideal target for α-amino acid ester prodrugs with relatively labile leaving groups while it is relatively inactivate toward amide prodrugs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.