A multivalent HIV-1 fusion inhibitor based on small helical foldamers

Cristian Guarise, Sandip Shinde, Karen Kibler, Giovanna Ghirlanda, Leonard J. Prins, Paolo Scrimin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The peptide sequence AcNH-TEG-Glu-Aib-Trp-AibAib-Trp-AibAib-Ile-Asp-OH (1), designed to display the WWI epitope found near the C-terminus of gp41, an envelope glycoprotein decorating the surface of the HIV-1 virus, has been synthesized and proved to have a relevant content of helical conformation because of the presence of five α-aminoisobutyric acid (Aib) units. Three copies of it have been connected to a tripodal platform based on 2,4,6-triethylbenzene-1,3,5-trimethylamine. The tripodal template 2 is even more structured than 1 thus suggesting a significant interaction between the three sequences connected to the platform. Preliminary inhibition assays of HIV-mediated cell fusion indicated that while the single peptide 1 is inactive within the concentration range of our assay, when it is conjugated to the tripodal platform, it is moderately active. These promising results suggest that our approach constitute a valid alternative to those reported so far.

Original languageEnglish
Pages (from-to)4346-4352
Number of pages7
JournalTetrahedron
Volume68
Issue number23
DOIs
Publication statusPublished - Jun 10 2012

    Fingerprint

Keywords

  • 3 -Helix
  • HIV-1 inhibition
  • Peptide foldamer
  • Peptide template
  • α-Aminoisobutyric acid

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Guarise, C., Shinde, S., Kibler, K., Ghirlanda, G., Prins, L. J., & Scrimin, P. (2012). A multivalent HIV-1 fusion inhibitor based on small helical foldamers. Tetrahedron, 68(23), 4346-4352. https://doi.org/10.1016/j.tet.2012.03.078