C-peptide inhibitors of Ebola virus glycoprotein-mediated cell entry: effects of conjugation to cholesterol and side chain-side chain crosslinking.
C-peptide inhibitors of Ebola virus glycoprotein-mediated cell entry: effects of conjugation to cholesterol and side chain-side chain crosslinking.
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DOI：
10.1016/j.bmcl.2013.07.056
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发表时间：
2013-10-01
影响因子：
2.7
通讯作者：
Lai, Jonathan R.
中科院分区：
文献类型：
--
作者：
Higgins, Chelsea D.;Koellhoffer, Jayne F.;Chandran, Kartik;Lai, Jonathan R.
We previously described potent inhibition of Ebola virus entry by a ‘C-peptide’ based on the GP2 C-heptad repeat region (CHR) targeted to endosomes (‘Tat-Ebo’). Here, we report the synthesis and evaluation of C-peptides conjugated to cholesterol, and Tat-Ebo analogs containing covalent side chain–side chain crosslinks to promote α-helical conformation. We found that the cholesterol-conjugated C-peptides were potent inhibitors of Ebola virus glycoprotein (GP)-mediated cell entry (~103-fold reduction in infection at 40 µM). However, this mechanism of inhibition is somewhat non-specific because the cholesterol-conjugated peptides also inhibited cell entry mediated by vesicular stomatitis virus glycoprotein G. One side chain–side chain crosslinked peptide had moderately higher activity than the parent compound Tat-Ebo. Circular dichroism revealed that the cholesterol-conjugated peptides unexpectedly formed a strong α-helical conformation that was independent of concentration. Side chain–side chain crosslinking enhanced α-helical stability of the Tat-Ebo variants, but only at neutral pH. These result provide insight into mechanisms of C-peptide inhibiton of Ebola virus GP-mediated cell entry.
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影响因子：
6.7
作者：
Porotto M;Rockx B;Yokoyama CC;Talekar A;Devito I;Palermo LM;Liu J;Cortese R;Lu M;Feldmann H;Pessi A;Moscona A
通讯作者：
Moscona A
影响因子：
5.4
作者：
Porotto, Matteo;Yokoyama, Christine C.;Moscona, Anne
通讯作者：
Moscona, Anne
DOI：
10.1074/jbc.m110.207084
发表时间：
2011-05-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Miller EH;Harrison JS;Radoshitzky SR;Higgins CD;Chi X;Dong L;Kuhn JH;Bavari S;Lai JR;Chandran K
通讯作者：
Chandran K
影响因子：
16
作者：
Weissenhorn, W;Carfi, A;Wiley, DC
通讯作者：
Wiley, DC
影响因子：
5.6
作者：
Cardoso, Rosa M. F.;Brunel, Florence M.;Wilson, Ian A.
通讯作者：
Wilson, Ian A.