Panclicins, novel pancreatic lipase inhibitors. I. Taxonomy, fermentation, isolation and biological activity.
Panclicins A, B, C, D, and E are novel pancreatic lipase inhibitors isolated from Streptomyces sp. NR 0619. Structurally, panclicins A, B, C, D, and E are analogues of tetrahydrolipstatin (THL), which contains a beta-lactone and a N-formyl leucine ester, and the IC50s of panclicins A, B, C, D, and E for porcine pancreatic lipase are 2.9, 2.6, 0.62, 0.66, and 0.89 microM, respectively. The potency of the inhibitory activity of each compound is attributed to the amino acid moiety of each structure. The panclicins are either glycine-type compounds such as panclicins C, D, E, which are two to threefold more potent than THL, or they are alanine-type compounds such as panclicins A and B, which are less potent than the glycine compounds. The inhibitory profiles of the panclicins for other lipases such as post-heparin plasma lipases and bacterial lipases are similar to those for pancreatic lipase. Panclicins A, B, C, D, and E, in a manner similar to THL, irreversibly inhibit pancreatic lipase. However, the compounds don't irreversibly inhibit the enzyme as strongly as THL does.
Nippon Roche Research Center, Kanagawa, Japan.
M
M
Mutoh
N
N
Nakada
S
S
Matsukuma
S
S
Ohshima
K
K
Yoshinari
J
J
Watanabe
M
M
Arisawa
D000818:Animals; D005285:Fermentation; D007783:Lactones / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D008049:Lipase / Q000037:antagonists & inhibitors*; D008066:Lipolysis; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D010179:Pancreas / Q000201:enzymology*; D013302:Streptomyces / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D013552:Swine
D007783:Lactones; D008049:Lipase