Fluostatins A and B, new inhibitors of dipeptidyl peptidase III, produced by Streptomyces sp. TA-3391. I. Taxonomy of producing strain, production, isolation, physico-chemical properties and biological properties.
New inhibitors of dipeptidyl peptidaseIII (EC 3.4.14.4) from human placenta, designated as fluostatins A and B, were discovered in the fermentation broth of a strain isolated in our institute. The strain has been identified as Streptomyces sp. TA-3391 on the basis of taxonomic studies. Fluostatins A and B were purified by Diaion HP-20 chromatography, ethyl acetate extraction, silica gel chromatography and reverse phase preparative HPLC. With the synthetic substrate, arginyl-arginine-2-naphthylamide, the IC50 values of fluostatins A and B were 0.44 and 24.0 micrograms/ml, respectively. Fluostatins A and B were slightly inhibitory against other dipeptidyl peptidases. Fluostatin A showed mixed-type (competitive and noncompeptitive) inhibition with human leucine-enkephalin as a substrate, and the inhibition constant (Ki) was 14.2 microM.
Institute of Microbial Chemistry, Tokyo, Japan.
T
T
Akiyama
S
S
Harada
F
F
Kojima
Y
Y
Takahashi
C
C
Imada
Y
Y
Okami
Y
Y
Muraoka
T
T
Aoyagi
T
T
Takeuchi
D002851:Chromatography, High Pressure Liquid; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D005285:Fermentation; D006801:Humans; D011500:Protein Synthesis Inhibitors / Q000737:chemistry* / Q000302:isolation & purification*; D012988:Soil Microbiology; D013302:Streptomyces / Q000145:classification / Q000378:metabolism*
D011500:Protein Synthesis Inhibitors; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100152:dipeptidyl peptidase III