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