Enzymatic synthesis of dehydro cyclo(His-Phe)s, analogs of the potent cell cycle inhibitor, dehydrophenylahistin, and their inhibitory activities toward cell division.
Cyclo(His-Phe) was effectively converted to its dehydro derivatives by the enzyme of Streptomyces albulus KO-23, an albonoursin-producing actinomycete. Two types of dehydro derivatives were isolated from the reaction mixture and identified as cyclo(DeltaHis-DeltaPhe) and cyclo(His-DeltaPhe). This is the first report on cyclo(His-DeltaPhe) and the enzymatic preparation of both compounds. Cyclo(DeltaHis-DeltaPhe), a tetradehydro cyclic dipeptide, exhibited a minimum inhibitory concentration of 0.78 mumol/ml inhibitory activity toward the first cleavage of sea urchin embryos, in contrast to cyclo(His-DeltaPhe) that had no activity. The finding that the isoprenylated derivative of cyclo(DeltaHis-DeltaPhe), dehydrophyenylahistin, had 2,000 times higher activity than cyclo(DeltaHis-DeltaPhe) indicates that an isoprenyl group attached to an imidazole ring of the compound was essential for the inhibitory activity.
Kanzaki
Hiroshi
H
Laboratory of Bioresources Chemistry, Faculty of Agriculture, Okayama University, Japan. hkanzki@cc.okayama-u.ac.jp
Yanagisawa
Satohiro
S
Nitoda
Teruhiko
T
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010879:Piperazines / Q000138:chemical synthesis*; D012617:Sea Urchins; D021241:Spectrometry, Mass, Electrospray Ionization; D013302:Streptomyces / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D010456:Peptides, Cyclic; D010879:Piperazines; C472173:dehydrophenylahistin