Enzymatic Synthesis of Dehydro Cyclo(His-Phe)s, Analogs of the Potent Cell Cycle Inhibitor, Dehydrophenylahistin, and Their Inhibitory Activities toward Cell Division

Hiroshi Kanzaki, Satohiro Yanagisawa, Teruhiko Nitoda

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cyclo(His–Phe) was effectively converted to its dehydro derivatives by the enzyme of <I>Streptomyces albulus</I> KO-23, an albonoursin-producing actinomycete. Two types of dehydro derivatives were isolated from the reaction mixture and identified as cyclo(ΔHis–ΔPhe) and cyclo(His–ΔPhe). This is the first report on cyclo(His–ΔPhe) and the enzymatic preparation of both compounds. Cyclo(ΔHis–ΔPhe), a tetradehydro cyclic dipeptide, exhibited a minimum inhibitory concentration of 0.78 μmol/ml inhibitory activity toward the first cleavage of sea urchin embryos, in contrast to cyclo(His–ΔPhe) that had no activity. The finding that the isoprenylated derivative of cyclo(ΔHis–ΔPhe), dehydrophyenylahistin, had 2,000 times higher activity than cyclo(ΔHis–ΔPhe) indicates that an isoprenyl group attached to an imidazole ring of the compound was essential for the inhibitory activity.
Original languageEnglish
Pages (from-to)2341-2345
Number of pages5
JournalBioscience, Biotechnology and Biochemistry
Volume68
Issue number11
DOIs
Publication statusPublished - Nov 23 2004
Externally publishedYes

Fingerprint

histidylphenylalanine
Sea Urchins
Actinobacteria
Dipeptides
Streptomyces
Microbial Sensitivity Tests
Cell Division
Cell Cycle
Embryonic Structures
Cells
Derivatives
Enzymes
dehydrophenylahistin
imidazole
albonoursin

Keywords

  • dehydro cyclic dipeptide
  • enzymatic conversion
  • inhibitor for cell division
  • diketopiperazine
  • albonoursin

Cite this

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title = "Enzymatic Synthesis of Dehydro Cyclo(His-Phe)s, Analogs of the Potent Cell Cycle Inhibitor, Dehydrophenylahistin, and Their Inhibitory Activities toward Cell Division",
abstract = "Cyclo(His–Phe) was effectively converted to its dehydro derivatives by the enzyme of <I>Streptomyces albulus KO-23, an albonoursin-producing actinomycete. Two types of dehydro derivatives were isolated from the reaction mixture and identified as cyclo(ΔHis–ΔPhe) and cyclo(His–ΔPhe). This is the first report on cyclo(His–ΔPhe) and the enzymatic preparation of both compounds. Cyclo(ΔHis–ΔPhe), a tetradehydro cyclic dipeptide, exhibited a minimum inhibitory concentration of 0.78 μmol/ml inhibitory activity toward the first cleavage of sea urchin embryos, in contrast to cyclo(His–ΔPhe) that had no activity. The finding that the isoprenylated derivative of cyclo(ΔHis–ΔPhe), dehydrophyenylahistin, had 2,000 times higher activity than cyclo(ΔHis–ΔPhe) indicates that an isoprenyl group attached to an imidazole ring of the compound was essential for the inhibitory activity.",
keywords = "dehydro cyclic dipeptide, enzymatic conversion, inhibitor for cell division, diketopiperazine, albonoursin",
author = "Hiroshi Kanzaki and Satohiro Yanagisawa and Teruhiko Nitoda",
year = "2004",
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language = "English",
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TY - JOUR

T1 - Enzymatic Synthesis of Dehydro Cyclo(His-Phe)s, Analogs of the Potent Cell Cycle Inhibitor, Dehydrophenylahistin, and Their Inhibitory Activities toward Cell Division

AU - Kanzaki, Hiroshi

AU - Yanagisawa, Satohiro

AU - Nitoda, Teruhiko

PY - 2004/11/23

Y1 - 2004/11/23

N2 - Cyclo(His–Phe) was effectively converted to its dehydro derivatives by the enzyme of <I>Streptomyces albulus KO-23, an albonoursin-producing actinomycete. Two types of dehydro derivatives were isolated from the reaction mixture and identified as cyclo(ΔHis–ΔPhe) and cyclo(His–ΔPhe). This is the first report on cyclo(His–ΔPhe) and the enzymatic preparation of both compounds. Cyclo(ΔHis–ΔPhe), a tetradehydro cyclic dipeptide, exhibited a minimum inhibitory concentration of 0.78 μmol/ml inhibitory activity toward the first cleavage of sea urchin embryos, in contrast to cyclo(His–ΔPhe) that had no activity. The finding that the isoprenylated derivative of cyclo(ΔHis–ΔPhe), dehydrophyenylahistin, had 2,000 times higher activity than cyclo(ΔHis–ΔPhe) indicates that an isoprenyl group attached to an imidazole ring of the compound was essential for the inhibitory activity.

AB - Cyclo(His–Phe) was effectively converted to its dehydro derivatives by the enzyme of <I>Streptomyces albulus KO-23, an albonoursin-producing actinomycete. Two types of dehydro derivatives were isolated from the reaction mixture and identified as cyclo(ΔHis–ΔPhe) and cyclo(His–ΔPhe). This is the first report on cyclo(His–ΔPhe) and the enzymatic preparation of both compounds. Cyclo(ΔHis–ΔPhe), a tetradehydro cyclic dipeptide, exhibited a minimum inhibitory concentration of 0.78 μmol/ml inhibitory activity toward the first cleavage of sea urchin embryos, in contrast to cyclo(His–ΔPhe) that had no activity. The finding that the isoprenylated derivative of cyclo(ΔHis–ΔPhe), dehydrophyenylahistin, had 2,000 times higher activity than cyclo(ΔHis–ΔPhe) indicates that an isoprenyl group attached to an imidazole ring of the compound was essential for the inhibitory activity.

KW - dehydro cyclic dipeptide

KW - enzymatic conversion

KW - inhibitor for cell division

KW - diketopiperazine

KW - albonoursin

U2 - 10.1271/bbb.68.2341

DO - 10.1271/bbb.68.2341

M3 - Article

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VL - 68

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JO - Bioscience, Biotechnology and Biochemistry

JF - Bioscience, Biotechnology and Biochemistry

SN - 0916-8451

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ER -