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Phosphinate Inhibitors of UDP‐ N ‐Acetylmuramoyl‐ L ‐Alanyl‐ D ‐Glutamate: L ‐Lysine Ligase (MurE)
Author(s) -
Štrancar Katja,
Boniface Audrey,
Blanot Didier,
Gobec Stanislav
Publication year - 2007
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200600191
Subject(s) - dna ligase , peptidoglycan , phosphinate , chemistry , biochemistry , ubiquitin ligase , lysine , enzyme , ubiquitin , amino acid , gene , organic chemistry , fire retardant
The increasing emergence of pathogenic bacterial strains with high resistance to antibiotic therapy has created an urgent need for the development of new antibacterial agents that are directed towards novel targets. We have focused our attention on the Mur ligases (MurC‐F), which catalyze the early steps of bacterial peptidoglycan biosynthesis, and which to date represent under‐exploited targets for antibacterial drug design. We show that some of our phosphinate inhibitors of UDP‐ N ‐acetylmuramoyl‐ L ‐alanyl: D ‐glutamate ligase (MurD) also inhibits UDP‐ N ‐acetylmuramoyl‐ L ‐alanyl‐ D ‐glutamate: L ‐lysine ligase (MurE). To obtain new information on their structure‐activity relationships, three new, structurally related phosphinates were synthesized and evaluated for inhibition of MurD and MurE.