Functional analysis of backbone cyclic peptides bearing the arm domain of the HIV-1 Rev protein: characterization of the karyophilic properties and inhibition of Rev-induced gene expression

Biochemistry. 2005 Aug 30;44(34):11555-66. doi: 10.1021/bi050752b.


This work describes the synthesis and activity of a novel backbone cyclic (BC) peptide library based on the sequence of the HIV-1 Rev arginine-rich motif (ARM). All the peptides in the library possess the same sequence but differ in their ring-moiety properties. The BC peptides were synthesized using simultaneous multiple-peptide synthesis and were fully assembled using bis(trichloromethyl)carbonate as a coupling agent. All the peptides in the library had inhibitory effects on the binding of Rev-GFP to importin beta in vitro. Studies performed with one of the BC Rev-ARM analogues, Rev-13, demonstrated that, like its parental linear peptide, it is karyophilic; i.e., it is able to mediate the nuclear import of conjugated bovine serum albumin (BSA) molecules. The cell penetrating properties of the BC peptides were assessed utilizing an ELISA-based system. This assay provides a quantitative evaluation of cell penetration. Most of the peptides from the library were able to penetrate intact Colo-205 cells to varying degrees. Furthermore, these BC peptides were able to carry BSA into intact Colo-205 cells. In addition to its cell penetrating and binding properties, the BC Rev-13 analogue inhibited Rev-induced gene expression in HeLa cells by 60-70% in the low micromolar range and exhibited no cell toxicity. The potential of BC peptides bearing ARM domains as lead compounds for the production of anti-HIV drugs is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arginine
  • Binding Sites
  • Gene Expression Regulation, Viral* / drug effects
  • Gene Products, rev / chemistry*
  • Gene Products, rev / genetics*
  • Gene Products, rev / metabolism
  • Guanosine Triphosphate / metabolism
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • HeLa Cells
  • Humans
  • Peptide Library
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / pharmacology
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • rev Gene Products, Human Immunodeficiency Virus


  • Gene Products, rev
  • Peptide Library
  • Peptides, Cyclic
  • Recombinant Proteins
  • rev Gene Products, Human Immunodeficiency Virus
  • Guanosine Triphosphate
  • Arginine