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

HIV Fusion Inhibitors
Aminoisobutyric Acids
HIV-1
Assays
Fusion reactions
Peptides
Cell Fusion
Membrane Glycoproteins
Viruses
Conformations
Epitopes
HIV

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

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

A multivalent HIV-1 fusion inhibitor based on small helical foldamers. / Guarise, Cristian; Shinde, Sandip; Kibler, Karen; Ghirlanda, Giovanna; Prins, Leonard J.; Scrimin, Paolo.

In: Tetrahedron, Vol. 68, No. 23, 10.06.2012, p. 4346-4352.

Research output: Contribution to journalArticle

Guarise, C, Shinde, S, Kibler, K, Ghirlanda, G, Prins, LJ & Scrimin, P 2012, 'A multivalent HIV-1 fusion inhibitor based on small helical foldamers', Tetrahedron, vol. 68, no. 23, pp. 4346-4352. https://doi.org/10.1016/j.tet.2012.03.078
Guarise, Cristian ; Shinde, Sandip ; Kibler, Karen ; Ghirlanda, Giovanna ; Prins, Leonard J. ; Scrimin, Paolo. / A multivalent HIV-1 fusion inhibitor based on small helical foldamers. In: Tetrahedron. 2012 ; Vol. 68, No. 23. pp. 4346-4352.
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