Abstract
The RP dipeptide motif is highly conserved in the third hypervariable region (V3 loop) of the extracellular envelope glycoprotein of different types of HIV isolates. In view of this, we have designed and synthesized a construction referred to as "template assembled synthetic peptide" (TASP), in which a lysine-rich short polypeptide was used as a template to covalently anchor arrays of tripeptides, such as RPR, RPK, or KPR. The pentavalent presentation, 5(RPR)-, 5(RPK)-, or 5(KPR)-TASP, molecules manifested maximum inhibitory activity on HIV infection with a 50% inhibitory concentration value of 1-5 microM, respectively. Structure and inhibitory-activity relationship studies using analogs of 5(KPR)-TASP indicated that the positively charged side chains of the K and R residues in the tripeptide molecules are critical for the optimal inhibitory activity of the pentavalent construct. Interestingly, replacement of L-amino acid residues by D-amino acids or reduction of the peptide bond between the first two amino acids of the tripeptide generated peptide-TASP analogs active at sub-microM, concentrations. The anti-HIV action of the peptide-TASP constructs is specific, since they inhibit infection of several types of CD4-expressing cel...Continue Reading
Citations
Feb 14, 2006·Cell Research·Ara G Hovanessian
Mar 10, 2000·AIDS Research and Human Retroviruses·S NisoleA G Hovanessian
Mar 19, 1999·AIDS Research and Human Retroviruses·N SeddikiA G Hovanessian
Apr 25, 2000·Journal of Virology·S Le BorgneY Rivière
Sep 15, 2005·Journal of Virology·Liwen YouThorsteinn Rögnvaldsson
Aug 5, 2011·BMC Cancer·Bernard KrustAra G Hovanessian
Jan 5, 2011·PloS One·Ara G HovanessianBernard Krust
Nov 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·B KrustL Edelman
Jul 17, 1999·The Journal of Peptide Research : Official Journal of the American Peptide Society·M MoulardJ M Sabatier
Nov 26, 2008·Experimental Cell Research·Marie-Estelle LosfeldDominique Legrand
Aug 8, 2006·Chembiochem : a European Journal of Chemical Biology·Yashveer SinghPascal Dumy
Sep 26, 2006·The FEBS Journal·Daniel E AleteAndrew W Stoker
Aug 26, 1998·Virology·R BarboucheE Fenouillet
Nov 13, 2004·Immunity·Ara G HovanessianBernard Krust
Jun 25, 1998·Experimental Cell Research·C CallebautA G Hovanessian
Nov 3, 2010·Biochimie·Bernard KrustAra G Hovanessian
Mar 30, 2001·Virology·C CallebautA G Hovanessian
Mar 25, 2014·PloS One·Mohamed S TahaMohammad R Ahmadian
Jun 11, 1999·Journal of Peptide Science : an Official Publication of the European Peptide Society·P Veprek, J Jezek
Aug 15, 1998·The Journal of Biological Chemistry·C CallebautA G Hovanessian
Jul 31, 2002·The Journal of Biological Chemistry·Elias A SaidAra G Hovanessian
Sep 17, 1999·The Journal of Biological Chemistry·S NisoleA G Hovanessian
Mar 14, 1997·The Journal of Biological Chemistry·C CallebautA G Hovanessian
Mar 29, 2002·The Journal of Biological Chemistry·Sébastien NisoleAra G Hovanessian
Dec 1, 1998·The Journal of Peptide Research : Official Journal of the American Peptide Society·R BarboucheJ M Sabatier
Jul 5, 2019·Drug Discovery Today·Sofia RomanoJoão Nuno Moreira
Apr 2, 1998·Experimental Cell Research·S BesseA G Hovanessian
Oct 29, 1997·Journal of Virology·A ValenzuelaA G Hovanessian
Jul 3, 2021·Cancers·Fabio RaineriIlaria Cascone