Chemical Approaches for Understanding and Controlling Infectious Diseases

  • Hirokazu Arimoto
Conference paper


Vancomycin and its related glycopeptide antibiotics are known for their therapeutic importance against methicillin-resistant Staphylococcus aureus(MRSA). Unfortunately, vancomycin-resistant enterococci (VRE) have emerged as an important nosocomial pathogen worldwide, and recently vancomycin-resistant Staphylococcus aureus(VRSA) acquired the vanA-resistant gene from VRE.


Cell Wall Synthesis Peptidoglycan Biosynthesis Cross Metathesis Lipid Intermediate Cell Wall Precursor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author is grateful to collaborators in Tohoku University and Shionogi & Co., Ltd., whose names appear in the references, for their hard work, creativity, and superb research skills. This work was supported in part by Grants-in-Aid for Scientific Research from MEXT, Japan (Nos. 17035039, 18032010, and 21310136) and by funds from the Uehara Memorial Foundation.


  1. 1.
    Arimoto H, Nishimura K, Kinumi T, Hayakawa I, Uemura D (1999) Multivalent polymer of vancomycin: enhanced antibacterial activity against VRE. J Chem Soc Chem Commun 1999:1361–1362Google Scholar
  2. 2.
    Lu J, Yoshida O, Hayashi S, Arimoto H (2007) Synthesis of rigidly-linked vancomycin dimers and their in vivo efficacy against resistant bacteria. Chem Commun (Camb) 2007:251–253CrossRefGoogle Scholar
  3. 3.
    Miura K, Yamashiro H, Uotani K, Kojima S, Yutsudo T, Lu J, Yoshida O, Yamano Y, Maki H, Arimoto H (2010) Mode of action of Van-M-02, a novel glycopeptide inhibitor of peptidoglycan synthesis, in vancomycin-resistant bacteria. Antimicrob Agents Chemother 54:960–962CrossRefPubMedGoogle Scholar
  4. 4.
    Nakama Y, Yoshida O, Yoda M, Araki K, Sawada Y, Nakamura J, Xu S, Miura K, Maki H, Arimoto H (2010) Discovery of a novel series of semisynthetic vancomycin derivatives ­effective against vancomycin-resistant bacteria. J Med Chem 53:2528–2533CrossRefPubMedGoogle Scholar
  5. 5.
    Sundram UN, Griffin JH, Nicas TI (1996) Novel vancomycin dimers with activity against ­vancomycin-resistant enterococci. J Am Chem Soc 118:13107–13108CrossRefGoogle Scholar
  6. 6.
    Griffin JH, Linsell MS, Nodwell MB, Chen QQ, Pace JL, Quast KL, Krause KM, Farrington L, Wu TX, Higgins DL, Jenkins TE, Christensen BG, Judice JK (2003) Multivalent drug design. Synthesis and in vitro analysis of an array of vancomycin dimers. J Am Chem Soc 125: 6517–6531CrossRefPubMedGoogle Scholar
  7. 7.
    Yoshida O, Nakamura J, Yamashiro H, Miura K, Hayashi S, Umetsu K, Xu S, Maki H, Arimoto H (2011) New insight into the mode of action of vancomycin dimers in bacterial cell wall ­synthesis. Med Chem Commun 2:278–282CrossRefGoogle Scholar
  8. 8.
    Rao JH, Whitesides GM (1997) Tight binding of a dimeric derivative of vancomycin with dimeric L-Lys-D-Ala-D-Ala. J Am Chem Soc 119:10286–10290CrossRefGoogle Scholar
  9. 9.
    Jain RK, Trias J, Ellman JA (2003) D-Ala-D-Lac binding is not required for the high activity of vancomycin dimers against vancomycin. J Am Chem Soc 125:8740–8741CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2012

Authors and Affiliations

  1. 1.Graduate School of Life SciencesTohoku UniversitySendaiJapan

Personalised recommendations