title: Inhibition of nuclear import by backbone cyclic peptidomimetics derived from the HIV-1 MA NLS sequence.
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.
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, Hebrew University of Jerusalem, Israel.
authors.forename: Elana
authors.initials: E
authors.lastname: Hariton-Gazal
authors.forename: Dorit
authors.initials: D
authors.lastname: Friedler
authors.forename: Assaf
authors.initials: A
authors.lastname: Friedler
authors.forename: Nehama
authors.initials: N
authors.lastname: Zakai
authors.forename: Chaim
authors.initials: C
authors.lastname: Gilon
authors.forename: Abraham
authors.initials: A
authors.lastname: Loyter
mesh_terms: D015683:Gene Products, gag / Q000737:chemistry*; D015488:HIV Antigens / Q000737:chemistry*; D006801:Humans; D019913:Nuclear Localization Signals / Q000037:antagonists & inhibitors*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014357:Trypsin; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D028901:alpha Karyopherins / Q000737:chemistry; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D015683:Gene Products, gag; D015488:HIV Antigens; D019913:Nuclear Localization Signals; D010456:Peptides, Cyclic; D014764:Viral Proteins; D028901:alpha Karyopherins; D054301:gag Gene Products, Human Immunodeficiency Virus; C087978:karyopherin alpha 2; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D012710:Serum Albumin, Bovine; D014357:Trypsin