Abstract: The invention provides new methods for screening libraries of peptides and other compounds for a desired property in eucaryotic cells. The methods are premised, in part, on the unexpected observation that the contents of procaryotic or lower eucaryotic cells, such as yeast, can be transferred to recipient eucaryotic cells in an essentially clonal manner by protoplast fusion of the respective cells. Applications of the methods include screening peptides in eucaryotic cells substantially incapable of episomal replication of transferred nucleic acid fragments; screening in eucaryotic cells peptides or secondary metabolites produced in procaryotic cells; and screening a library of peptides for capacity to bind a selected RNA in eucaryotic cells.

Abstract: Compositions and methods for identifying compositions which inhibit binding of the Rev protein to the Rev-responsive element in cells infected by HIV-1 are provided. The compositions display or mimic the electronic configuration of a binding domain within the native Rev protein, but are free from those portions responsible for REV activity and are preferably modified to display enhanced binding affinity to the RRE. Screening methods for identifying polypeptides and other compositions having such enhanced binding affinity are also described.