Correlation Between Shiftide Activity and HIV-1 Integrase Inhibition by a Peptide Selected from a Combinatorial Library

Ayelet Armon-Omer, Aviad Levin, Zvi Hayouka, Karin Butz, Felix Hoppe-Seyler, Shoshana Loya, Amnon Hizi, Assaf Friedler, Abraham Loyter

Research output: Contribution to journalArticlepeer-review


The human immunodeficiency virus type 1 (HIV-1) integrase (IN) protein is an emerging target for the development of anti-HIV drugs. We recently described a new approach for inhibiting IN by "shiftides"-peptides that inhibit the protein by shifting its oligomerization equilibrium from the active dimer to the inactive tetramer. In this study, we used the yeast two-hybrid system with the HIV-1 IN as a bait and a combinatorial peptide aptamer library as a prey to select peptides of 20 amino acids that specifically bind IN. Five non-homologous peptides, designated as IN-1 to IN-5, were selected. ELISA studies confirmed that IN binds the free peptides. All the five peptides interact with IN with comparable affinity (Kd≈10 μM), as was revealed by fluorescence anisotropy studies. Only one peptide, IN-1, inhibited the enzymatic activity of IN in vitro and the HIV-1 replication in cultured cells. In correlation, fluorescence anisotropy binding experiments revealed that of the five peptides, only the inhibitory IN-1 inhibited the DNA binding of IN. Analytical gel filtration experiments revealed that only the IN-1 and not the four other peptides shifted the oligomerization equilibrium of IN towards the tetramer. Thus, the results show a distinct correlation between the ability of the selected peptides to inhibit IN activity and that to shift its oligomerization equilibrium.

Original languageEnglish
Pages (from-to)971-982
Number of pages12
JournalJournal of Molecular Biology
Issue number4
StatePublished - 29 Feb 2008


  • HIV-1
  • fluorescence anisotropy
  • integrase
  • synthetic peptides
  • yeast two-hybrid


Dive into the research topics of 'Correlation Between Shiftide Activity and HIV-1 Integrase Inhibition by a Peptide Selected from a Combinatorial Library'. Together they form a unique fingerprint.

Cite this