Vinylogous Amide Analogues of Diaminopimelic Acid (DAP) as Inhibitors of Enzymes Involved in Bacterial Lysine Biosynthesis

Jennifer F. Caplan, Renjian Zheng, John S. Blanchard, John C. Vederas

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Equation Presented Vinylogous amides 5 and 6 have been synthesized from L-propargyl glycine and tested against diaminopimelate (DAP) enzymes involved in bacterial lysine biosynthesis. Both are reversible inhibitors of DAP D-dehydrogenase and DAP epimerase with IC50 values in the 500 μM range. Compound 5 shows competitive inhibition against the L-dihydrodipicolinate (DHDP) reductase with a Ki value of 32 μM, which is comparable to the planar dipicolinate 16 (Ki = 26 μM), the best known inhibitor of the enzyme.

Original languageEnglish (US)
Pages (from-to)3857-3860
Number of pages4
JournalOrganic Letters
Volume2
Issue number24
StatePublished - Nov 30 2000

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diaminopimelate epimerase
Dihydrodipicolinate Reductase
Diaminopimelic Acid
biosynthesis
lysine
Biosynthesis
Enzyme Inhibitors
Amides
Glycine
inhibitors
amides
Inhibitory Concentration 50
Lysine
enzymes
Oxidoreductases
analogs
acids
dehydrogenases
Enzymes
glycine

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Vinylogous Amide Analogues of Diaminopimelic Acid (DAP) as Inhibitors of Enzymes Involved in Bacterial Lysine Biosynthesis. / Caplan, Jennifer F.; Zheng, Renjian; Blanchard, John S.; Vederas, John C.

In: Organic Letters, Vol. 2, No. 24, 30.11.2000, p. 3857-3860.

Research output: Contribution to journalArticle

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