Abstract
[reaction: see text] 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 IC(50) values in the 500 microM range. Compound 5 shows competitive inhibition against the L-dihydrodipicolinate (DHDP) reductase with a K(i) value of 32 microM, which is comparable to the planar dipicolinate 16 (K(i) = 26 microM), the best known inhibitor of the enzyme.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amides / chemical synthesis
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Amides / chemistry
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Amino Acid Isomerases / antagonists & inhibitors
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Amino Acid Oxidoreductases / antagonists & inhibitors
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Bacteria / chemistry*
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Bacteria / metabolism
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Diaminopimelic Acid / analogs & derivatives*
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Diaminopimelic Acid / chemical synthesis*
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Diaminopimelic Acid / chemistry
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Dihydrodipicolinate Reductase
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Lysine / biosynthesis*
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Oxidoreductases / antagonists & inhibitors
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Oxidoreductases Acting on CH-CH Group Donors*
Substances
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Amides
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Anti-Bacterial Agents
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Enzyme Inhibitors
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Diaminopimelic Acid
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Oxidoreductases
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Dihydrodipicolinate Reductase
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Oxidoreductases Acting on CH-CH Group Donors
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Amino Acid Oxidoreductases
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diaminopimelate dehydrogenase
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Amino Acid Isomerases
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diaminopimelate epimerase
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Lysine