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

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 (US)
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
State	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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10.1016/j.tet.2012.03.078

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title = "A multivalent HIV-1 fusion inhibitor based on small helical foldamers",

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.",

keywords = "3 -Helix, HIV-1 inhibition, Peptide foldamer, Peptide template, α-Aminoisobutyric acid",

author = "Cristian Guarise and Sandip Shinde and Karen Kibler and Giovanna Ghirlanda and Prins, {Leonard J.} and Paolo Scrimin",

note = "Funding Information: This work was supported in part by NSF Career Award 0449842 to G.G. L.J.P. acknowledges financial support from the ERC (contract UE-239898). We thank the National Institutes of Health AIDS Research and Reference Reagent Program for providing non-commercial reagents. The Padova group gratefully acknowledges the support by MIUR (grant 2006039071 ) and by the University of Padova (starting grant to L.J.P.). ",

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AU - Guarise, Cristian

AU - Shinde, Sandip

AU - Kibler, Karen

AU - Ghirlanda, Giovanna

AU - Prins, Leonard J.

AU - Scrimin, Paolo

N1 - Funding Information: This work was supported in part by NSF Career Award 0449842 to G.G. L.J.P. acknowledges financial support from the ERC (contract UE-239898). We thank the National Institutes of Health AIDS Research and Reference Reagent Program for providing non-commercial reagents. The Padova group gratefully acknowledges the support by MIUR (grant 2006039071 ) and by the University of Padova (starting grant to L.J.P.).

PY - 2012/6/10

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N2 - 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.

AB - 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.

KW - 3 -Helix

KW - HIV-1 inhibition

KW - Peptide foldamer

KW - Peptide template

KW - α-Aminoisobutyric acid

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

Abstract

Keywords

ASJC Scopus subject areas

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