Binding of external ligands onto an engineered virus capsid.
The development of novel delivery systems for therapeutic substances includes targeting of the carriers to a specific site or tissue within the body of the recipient. This can be accomplished by appropriate receptor-binding domains and requires linking of these domains to the carrier. We have used recombinantly expressed polyomavirus-like particles as a model system and inserted the sequence of a WW domain into different surface loops of the viral capsid protein VP1. In one variant, the WW domain maintained its highly selective binding properties of proline-rich ligands and showed an increased affinity but also an accelerated association/dissociation equilibrium compared to the isolated WW domain, thus allowing a short-term coupling of external ligands onto the surface of the virus-like particles.
Schmidt
U
U
Institut für Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle, Germany. ulis@ichr.uwa.edu.au
Rudolph
R
R
Böhm
G
G
D000818:Animals; D002213:Capsid / Q000235:genetics / Q000378:metabolism*; D036022:Capsid Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D003001:Cloning, Molecular; D050556:Fatty Acid-Binding Proteins; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D011120:Polyomavirus / Q000502:physiology; D011392:Proline / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D036022:Capsid Proteins; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; C106410:Fnbp1 protein, mouse; D008024:Ligands; D011993:Recombinant Fusion Proteins; C062481:VP1 protein, polyomavirus; D011392:Proline