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

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

doi:10.1016/j.tet.2012.03.078

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

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

Arizona State University

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	4346-4352
Number of pages	7
Journal	Tetrahedron
Volume	68
Issue number	23
DOIs	https://doi.org/10.1016/j.tet.2012.03.078
Publication status	Published - Jun 10 2012

Keywords

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

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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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

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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.",

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AU - Guarise, Cristian

AU - Shinde, Sandip

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AU - Ghirlanda, Giovanna

AU - Prins, Leonard J.

AU - Scrimin, Paolo

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