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 | |
| Publication status | Published - Jun 10 2012 |
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Keywords
- α-Aminoisobutyric acid
- 3 -Helix
- HIV-1 inhibition
- Peptide foldamer
- Peptide template
ASJC Scopus subject areas
- Biochemistry
- Organic Chemistry
- Drug Discovery
Cite this
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 journal › Article
}
TY - JOUR
T1 - A multivalent HIV-1 fusion inhibitor based on small helical foldamers
AU - Guarise, Cristian
AU - Shinde, Sandip
AU - Kibler, Karen
AU - Ghirlanda, Giovanna
AU - Prins, Leonard J.
AU - Scrimin, Paolo
PY - 2012/6/10
Y1 - 2012/6/10
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 - α-Aminoisobutyric acid
KW - 3 -Helix
KW - HIV-1 inhibition
KW - Peptide foldamer
KW - Peptide template
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U2 - 10.1016/j.tet.2012.03.078
DO - 10.1016/j.tet.2012.03.078
M3 - Article
AN - SCOPUS:84860699775
VL - 68
SP - 4346
EP - 4352
JO - Tetrahedron
JF - Tetrahedron
SN - 0040-4020
IS - 23
ER -