title: Lactate cannot substitute for alanine in d4T-based anti-HIV nucleotide prodrugs--despite efficient esterase-mediated hydrolysis.
abstract: As part of our on-going effort to deliver masked phosphates of antiviral nucleosides inside living cells we have previously discovered that amino acid-derived phosphoramidates are particularly effective. Here we report that lactate analogues, with a simple change of bridging nitrogen for oxygen, are virtually inactive as antiviral agents and apparently do not achieve intracellular nucleoside phosphate delivery.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, UK. mcguigan@cardiff.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: McGuigan
authors.forename: D
authors.initials: D
authors.lastname: Cahard
authors.forename: C
authors.initials: C
authors.lastname: Ballatore
authors.forename: A
authors.initials: A
authors.lastname: Siddiqui
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D000409:Alanine; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004950:Esterases / Q000494:pharmacology*; D006868:Hydrolysis; D019344:Lactic Acid; D009711:Nucleotides / Q000494:pharmacology*; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D009711:Nucleotides; D011355:Prodrugs; D019344:Lactic Acid; D004950:Esterases; D000409:Alanine