R. Grabherr et W. Ernst, The Baculovirus expression system as a tool for generating diversity by viral surface display, COMB CHEM H, 4(2), 2001, pp. 185-192
Citations number
65
Categorie Soggetti
Chemistry & Analysis
Journal title
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
It has become a major goal of molecular biologists, biochemists, and immuno
logists to be able to modulate the structure of proteins, in order to incre
ase their antigenicity, alter their biological properties and/or explore th
eir function. Based on the concept of bacterial phage display, by which pro
teins are being selected and analyzed in conjunction with their genetic inf
ormation, eukaryotic systems have been investigated for their use in genera
ting biomolecular diversity. The advantage of posttranslational modificatio
n and the possible harbouring of structural complex proteins has lead scien
tists to include eukaryotic systems in the wide field of molecular design.
The ideal expression vectors for surface display are eukaryotic viruses, th
at allow large gene insertions, efficiently present foreign proteins on the
particle surface, are easy to propagate and, if possible, not pathogenic t
o humans. By inserting peptides into a native virus coat protein or by expr
essing foreign proteins as coat protein fusion proteins or linked to specif
ic anchor domains it becomes possible to display polypeptides of interest o
n the surface of replicating particles. A variety of different strategies a
re currently under investigation in order to utilize the baculovirus insect
cell expression system for efficient display on the surface of virus parti
cles as well as on the surface of virally infected insect cells. Increasing
the transfection efficiency, optimizing cloning procedures, and establishi
ng applicable selection methods have lead to the development of a powerful
tool for drug screening and ligand screening.