PANCLICINS, NOVEL PANCREATIC LIPASE INHIBITORS .1. TAXONOMY, FERMENTATION, ISOLATION AND BIOLOGICAL-ACTIVITY

Panclicins A, B, C, D, and E are novel pancreatic lipase inhibitors is olated 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 IC(50)s of pancli cins A, B, C, D, and E for porcine pancreatic lipase are 2.9, 2.6, 0.6 2, 0.66, and 0.89 mu M, respectively. The potency of the inhibitory ac tivity of each compound is attributed to the amino acid moiety of each structure. The panclicins are either glycine-type compounds such as p anclicins 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 th e panclicins for other lipases such as post-heparin plasma lipases and bacterial lipases are similar to those for pancreatic lipase. Panclic ins A, B, C, D, and E, in a manner similar to THL, irreversibly inhibi t pancreatic lipase. However, the compounds don't irreversibly inhibit the enzyme as strongly as THL does.