Synthesis and evaluation of inhibitors for Escherichia coli glucosamine-6-phosphate synthase

Computational and experimental evaluation of ornithine derivatives as ornithine decarboxylase inhibitors

“…This compound was proposed for study as an amino acid transporter and glucosamine-6-phosphate synthase. Then, considering that compound 6 has a structural relationship with compound 4 and that it has been used in some biological targets (Auvin et al, 1991;Larimore et al, 1980;Olomucki et al, 1971;Woodward and Kornberg, 1980), the authors decided to model and test it biologically. The inhibitory effects of 6 on ODC activity showed a K d value of 2.5 mM.…”

N-ω-chloroacetyl-l-ornithine, a new competitive inhibitor of ornithine decarboxylase, induces selective growth inhibition and cytotoxicity on human cancer cells versus normal cells

“…Computational docking simulations indicated that N-x-chloroacetyl-L-ornithine (NCAO) (Figure 1) should inhibit rat liver ODC with high affinity, and in vivo assays showed its potential properties for inhibiting cell proliferation with low toxicity. NCAO is an ornithine analogue that was originally proposed as a general yeast amino acid permease [27][28][29] and a possible Escherichia coli glucosamine-6-phosphate synthase inhibitor 30 . Based on the recent findings, 30 years of polyamine-related approaches to cancer therapy may finally bear fruit by developing an ODC inhibitor that has good potency, an attractive pharmacokinetic profile, and the ability to overcome cell resistance 3 .…”

From Lobry de Bruyn to enzyme-catalyzed ammonia channelling: molecular studies of D-glucosamine-6P synthase

“…This conclusion was drawn from studies with a model peptide based on the N-terminal sequence of the protein, which showed that, after inactivation, a cyclization reaction occurs with the free α-amino group of the N-terminal cysteine at slightly alkaline pH, resulting in a blocked N-terminus. 53 A similar mechanism occurs with the N 3 -haloacetyl derivatives of -diaminopropionate 54 and is likely to apply for GlmS inhibition by anticapsine.…”