Abstract
In the present work we have constructed a series of backbone cyclic peptides, which differed in the amino acid residues located at the C-terminal position of the previously described BCvir peptide (A. Friedler, N. Zakai, O. Karni, Y.C. Broder, L. Baraz, M. Kotler, A. Loyter, C. Gilon, Biochemistry 37 (1998)). BCvir is a cyclic peptide, derived from the nuclear localization signal (NLS) of the human immunodeficiency virus type 1 matrix protein. The majority of the cyclic peptides described here inhibited nuclear import in vitro. The most potent inhibitors were those bearing bulky hydrophobic amino acids such as Leu, Phe or Nal (naphthyl Ala) at the C-terminus. On the other hand, peptides bearing polar amino acid residues such as Asn, Cys or a reduced amide bond were not inhibitory. The present studies demonstrate the importance of a bulky hydrophobic C-terminal side chain and an exocyclic amide bond preceding it, to the inhibitory activity of the NLS-derived BC peptides. Being only inhibitory, these BC peptides resemble classic receptor antagonists.
| Original language | English |
|---|---|
| Pages (from-to) | 234-242 |
| Number of pages | 9 |
| Journal | Biochimica et Biophysica Acta - Protein Structure and Molecular Enzymology |
| Volume | 1594 |
| Issue number | 2 |
| DOIs | |
| State | Published - 11 Feb 2002 |
Bibliographical note
Funding Information:This work was supported by the Horowitz Foundation and by the German Israeli Foundation (grant No. I-590-105.09/98) (to A.L. and C.G.), and by the DA’AT consortium (to C.G.). The authors wish to thank Carina Hazan for computer modeling and to Gil Fridkin for helpful suggestions.
Keywords
- Antagonist
- Backbone cyclization
- Importin α
- Matrix protein
- Nuclear import
- Nuclear localization signal
