Document 0890
 DOCN  M9540890
 TI    Building zinc fingers by selection: toward a therapeutic application.
 DT    9504
 AU    Wu H; Yang WP; Barbas CF 3rd; Department of Molecular Biology, Scripps
       Research Institute, La; Jolla, CA 92037.
 SO    Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):344-8. Unique Identifier :
       AIDSLINE MED/95132595
 AB    A phage display approach was utilized to modify the specificity of each
       of the three fingers of the murine transcription factor Zif268.
       Selections were performed by using the consensus binding sequence of the
       natural protein and a conserved sequence in the genome of the type 1
       human immunodeficiency virus. By using an extensive randomization
       strategy, the entire 3-bp specificity of a finger has been changed.
       Rapid analysis of selected zinc fingers was facilitated by the
       development of an immunoscreening assay for DNA binding and specificity.
       To investigate the mechanism of binding and specificity, the binding
       kinetics of Zif268 and 10 selected variants were determined in real time
       with an assay based on surface plasmon resonance. Differential
       mechanisms for sequence-specific recognition were observed. No evidence
       in support of a single general coding relationship between zinc finger
       and target DNA sequence was observed. The prospects for the development
       of this class of proteins in human therapy are considered.
 DE    Animal  Base Sequence  Binding Sites/GENETICS  Comparative Study
       DNA-Binding Proteins/*GENETICS/METABOLISM/THERAPEUTIC USE  DNA,
       Viral/GENETICS/METABOLISM  Gene Library  Genetic Code  HIV-1/GENETICS
       Mice  Molecular Sequence Data  Peptide Fragments/*GENETICS/METABOLISM
       Protein Binding  Protein Engineering/*METHODS  Selection (Genetics)
       Sequence Analysis  Structure-Activity Relationship  Support, Non-U.S.
       Gov't  Transcription Factors/*GENETICS/METABOLISM/THERAPEUTIC USE  Zinc
       Fingers/*GENETICS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).