Designer Adhesin Technology

  • Klemm, Per (Project Manager)
  • Schembri, Mark (Project Participant)
  • Kjærgaard, Kristian (Project Participant)

    Project Details

    Description

    The ability of proteins to bind to specific molecules is of paramount importance for organisms in nature and a key factor in understanding and manipulating molecular processes. Natural bacterial adhesins recognize targets in a simple lock-and-key fashion. The receptor specificity is determined by the composition of the peptide segment(s) that constitute the binding domain. The specificity of bacterial adhesins has been selected to fit the requirements of the bacteria in nature. However, one might wish to create designer adhesins which bind to targets quite different from those selected for in nature, e.g. targets of biomedical interest, synthetic chemicals, pollutants, metals etc. Based on bacterial fimbriae we have created designer adhesins, either by display of random peptide libraries to create a huge number of chimeric proteins from which new adhesins can be selected; or by manipulation of the receptor site of the natural fimbrial adhesin.
    Type 1 fimbriae are bacterial surface organelles. A type 1 fimbriated bacterium is covered by 100-500 such organelles. A single type 1 fimbria is a heteropolymer of about 1000 proteins. We have used fimbriae to display heterologous peptides in connection with development of vaccine systems and displayed defined peptides conferring metal binding. Recently, we have used the fimbrial systems for display of random peptide libraries. In such vast numbers of different peptide combinations are displayed. The technology has a very broad range of applications and can in principle be used to select adhesins to any target molecule. We have demonstrated specific binding to nickel and copper. We are currently developing binders that specifically can bind to derivatives of toxic heavy metals, such as cadmium, lead, and mercury. These binders could be used in connection with detection systems for such metals or directly as biosorption agents for the removal of toxic metals from the environment.
    StatusFinished
    Effective start/end date01/05/199501/05/1998

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