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  • Poster presentation
  • Open Access

Improvement of Polybiguanide-based Microbicides Using Computational Design Methodologies

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Retrovirology20052 (Suppl 1) :P30

  • Published:


  • Nitrogen Atom
  • Electrostatic Potential
  • Design Methodology
  • Calculation Software
  • Biguanide

Polyethylene hexamethylene biguanide (PEHMB), a polybiguanide compound under development as a topical microbicide effective against HIV-1, was used as a starting point for rational design strategies and novel computational methods focused on identifying similar compounds with greater safety and activity. To investigate the hypothesis that PEHMB may represent a specific 3-D conformation and a degree of chain flexibility that confers the ability to inhibit HIV-1 infection through interactions with HIV-1 co-receptors, patented molecular calculation software (Shape Signatures) was used to predict bioisosteres of PEHMB. These analyses suggested that substitution of a bithiazole group for the ethylene spacers of PEHMB would provide backbone rigidity, nitrogen atom spacing, and electrostatic potentials similar to PEHMB. The resulting molecule, poly(hexamethylene-c-2, 2'-diamino-5, 5'-bithiazole (PHDB), was found to have similar cytotoxicity yet greater activity than PEHMB. These studies strongly support our strategy of design and synthesis of second-generation compounds based on the PEHMB motif.


Authors’ Affiliations

Department of Microbiology and Immunology, and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA
Novaflux Biosciences, Inc., Princeton, NJ, USA
University of Medicine and Dentistry of New Jersey, Piscataway, NJ


© The Author(s) 2005