MOLECULAR DESIGN AND SYNTHESIS OF A NEW CLASS OF TRIGGERED ENEDIYNE

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13672338
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 医薬分子機能学
• Research Institution: NATIONAL INSTITUTE OF HEALTH SCIENCES
• Principal Investigator: KURIHARA Masaaki NATIONAL INSTITUTE OF HEALTH SCIENCES, 有機化学部, 室長 (20205206)
• Project Period (FY): 2001 – 2002
• Keywords: enediyne / Bergman reaction / trigger / DNA cleavage / 光照射

Research Abstract

It is an interesting challenge to design alternate frameworks and triggering mechanisms, with the goal of producing a stable enediyne which can be activated under controlled conditions, especially in away which directs the cytotoxicity toward a specific pathogen or tissue.
I found simple trigger of cycloaromatization in enediyne system. This enediyne compound were activated by deprotection to cleave DNA.

Research Products

• [Publications] M.Oba, M.Tanaka, M.Kurihara, H.Suemune: "Conformation of Peptides Containing a Chiral α-Ethylated α,α-Disubstituted α-Amino Acid : (S)-EthylLeucine (= (2S)-2-Amino-2-ethyl-4-methylpentanoic Acid) within Sequences of Dimethylglycine and Diethylglycine Residues"Helv.Chim.Acta.. 85. 3197-3218 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Y.Suhara, A.Kittaka, K.Ono, M.Kurihara, T.Fujishima, A.Yoshida, H.Takayama: "Design and Efficient Synthesis of New Stable 1α,25-Dihydroxy-19-norvitamin D_3Analogues Containing Amide Bond"Bioorg.Med.Chem.Lett.. 12. 3533-3536 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T.Satoh, A.Itoga, Y.Isogai, M.Kurihara, S.Yamada, M.Natori, N.Suzuki, K.Suruga, R.Kawachi, M.: "Increasing the conformational stability by replacement of heme axial ligand in c-type cytochrome"FEBS letters. 531. 543-547 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] M.Kurihara, M.Tanaka, M.Oba, H.Suemune, N.Miyata: "Conformation of Oligopeptides Containing Chiral α,α-Disubstituted Amino Acids : Computational Study"Peptides Science 200. 287-288 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] A.Kittaka, M.Kurihara, S.Pelege, Y.Suhara, H.Takayama: "2α-(3-Hydroxypropyl)-and 2a-(3-Hydroxyproxy)-1a,25-vitamin D_3 Accessible to Vitamin D Receptor Mutant Related to Hereditary Vitamin D-Resistant Rickets"Chem.Pharm.Bull.. 51. 357-358 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] M.Kurihara, W.Hakamata: "Convenient Preparation of Cyclic Acetals Using Diols, TMS-source and a Catalytic Amount of TMSOTf"J.Org.Chem.. 68. 3413-3415 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] M. Oba, M. Tanaka, M. Kurihara, H. Suemune: "Conformation of Peptides Containing a Chiral α-Ethylated α,α-Disubstituted α-Amino Acid : (S)-EthylLeucine (=(2S)-2-Amino-2-ethyl-4-methylpentanoic Acid) within Sequences of Dimethylglycine and Diethylglycine Residues"Helv. Chim. Acta.. 85. 3197-3218 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Y. Suhara, A. Kittaka, K. Ono, M. Kurihara, T.Fujishima, A. Yoshida, H. Takayama: "Design and Efficient Synthesis of New Stable 1α,25-Dihydroxy- 19-norvitamin D3 Analogues Containing Amide Bond"Bioorg. Med. Chem. Lett.. 12. 3533-3536 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Natori, N. Suzuki, K. Suruga, R. Kawachi, M.Arahira, T. Nishio, C. Fukazawa, T. Oku, T. Satoh, A. Itoga, Y. Isogai, M. Kurihara, S. Yamada: "Increasing the conformational stability by replacement of heme axial ligand in c-type cytochrome"FEBS letters. 531. 543-547 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Kurihara, M. Tanaka, M. Oba, H. Suemune, N.Miyata: "Conformation of Oligopeptides Containing Chiral α,_α-Disubstituted Amino Acids : Computational Study"Peptide Science 2001. 287-288 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Kurihare, W. Hakamata: "Convenient Preparation of Cyclic Acetals Using Diols, TMS-source and a Catalytic Amount of TMSOTf"J. Org. Chem.. 68. 3413-3415 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] A. Kittaka, M. Kurihara, S. Peleg, Y. Suhara, H. Takayama: "2α-(3-Hydroxypropyl)- and 2α-(3-Hydroxypropoxy)-1α,25-vitamin D3 Accessible to Vitamin D Receptor Mutant Related to Hereditary Vitamin D-Resistant Rickets"Chem. Pharm.Bull.. 51. 357-358 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Kurihara, M. Tanaka, M. Oba, H. Suemune: "Conformational Study of Heteropeptide Prepared from Chiral α-Ethylated α, α-Disubstituted _-Amino Acids"Peptides 2002. 902-903 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Kurihara, Y. Sato, M. Tanaka, M. Oba, Y. Demizu,H. Suemune, H. Okuda: "Prediction of the helical screw sense of oligopeptides containing chiral alpha, alpha-disubstituted amino acids"Peptide Science 2002. 323-324 (2003)
  • Description: 「研究成果報告書概要(欧文)」より