4-Amino-6-methylhept-2-enoic acid: a leucine analogue and potential probe for localizing sites of proteolytic control in the hepatocyte.
A recent analysis of leucine analogues has suggested that the carboxyl group is not required for mediating low concentration proteolytic inhibition in liver cells. In designing a probe to localize the regulatory site(s), we tested this hypothesis by synthesizing an analogue with a 2-carbon insert between the carboxyl and alpha-carbon. The Wittig product, a trans olefin, was fully active. Surprisingly, low concentration activity was lost when the double bond was eliminated by hydrogenation although some inhibitory effectiveness at high concentrations was evident. Since the double bond extends the carboxyl group away from the alpha-carbon, the results support the above hypothesis as well as the feasibility of adding functional groups to the carboxyl end of leucine.
Wert
J J
JJ
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033.
Miotto
G
G
Kadowaki
M
M
Mortimore
G E
GE
D000818:Animals; D002478:Cells, Cultured; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship
D011480:Protease Inhibitors; C076143:4-amino-6-methylhept-2-enoic acid; D007930:Leucine