Isolation and structure of leukotriene-A4 hydrolase inhibitor: 8(S)-amino-2(R)-methyl-7-oxononanoic acid produced by Streptomyces diastaticus.
The novel amino acid 8(S)-amino-2(R)-methyl-7-oxononanoic acid (1) was isolated from the soil-borne microorganism Streptomyces diastaticus during our screening for inhibitors of leukotriene-A4 hydrolase (LTA4H), a requisite enzyme in the biosynthesis of the potent inflammatory mediator leukotriene-B4 (LTB4). The structure of 1 was determined by detailed spectroscopic analyses and is related to 7-keto-8-aminopelargonic acid (2), a biosynthetic precursor of biotin. The relative potency of 1 (LTA4H IC50 = 0.6 microM) warranted further biological studies.
Parnas
B L
BL
Searle Research and Development, Monsanto Company, St. Louis, Missouri 63198, USA.
Durley
R C
RC
Rhoden
E E
EE
Kilpatrick
B F
BF
Makkar
N
N
Thomas
K E
KE
Smith
W G
WG
Corley
D G
DG
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001710:Biotin / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005227:Fatty Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000097:blood; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism*; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000097:blood
C102483:8-amino-2-methyl-7-oxononanoic acid; D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D011480:Protease Inhibitors; D007975:Leukotriene B4; D013929:Thromboxane B2; D001710:Biotin; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase