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.
Akiyama
T
T
Institute of Microbial Chemistry, Tokyo, Japan.
Harada
S
S
Kojima
F
F
Takahashi
Y
Y
Imada
C
C
Okami
Y
Y
Muraoka
Y
Y
Aoyagi
T
T
Takeuchi
T
T
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