Abstract:
:Among the EGFRs, HER2 is a major heterodimer partner and also has important implications in the formation of particular tumors. Interaction of HER2 protein with other EGFR proteins can be modulated by small molecule ligands and, hence, these protein-protein interactions play a key role in biochemical reactions related to control of cell growth. A peptidomimetic (compound 5-1) that binds to HER2 protein extracellular domain and inhibits protein-protein interactions of EGFRs was conjugated with BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene). Conjugation of BODIPY to the peptidomimetic was investigated by different approaches. The conjugate was characterized for its ability to bind to HER2 overexpressing SKBR-3 and BT-474 cells. Furthermore, cellular uptake of conjugate of BODIPY was studied in the presence of membrane tracker and Lyso tracker using confocal microscopy. Our results suggested that fluorescently labeled compound 5-7 binds to the extracellular domain and stays in the membrane for nearly 24 h. After 24 h there is an indication of internalization of the conjugate. Inhibition of protein-protein interaction and downstream signaling effect of compound 5-1 was also studied by proximity ligation assay and Western blot analysis. Results suggested that compound 5-1 inhibit protein-protein interactions of HER2-HER3 and phosphorylation of HER2 in a time-dependent manner.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Banappagari S,McCall A,Fontenot K,Vicente MG,Gujar A,Satyanarayanajois Sdoi
10.1016/j.ejmech.2013.04.038subject
Has Abstractpub_date
2013-07-01 00:00:00pages
60-9eissn
0223-5234issn
1768-3254pii
S0223-5234(13)00270-5journal_volume
65pub_type
杂志文章abstract::A series of novel di- or trisubstituted isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by 1H NMR and 13C NMR as well as LC-MS. The anticancer activity of the fourty-three new isatin derivatives against human T lymphocyte cells Jurkat was evaluate...
journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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doi:10.1016/j.ejmech.2015.06.050
更新日期:2015-08-28 00:00:00
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2006.04.004
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journal_title:European journal of medicinal chemistry
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doi:10.1016/j.ejmech.2016.10.057
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journal_title:European journal of medicinal chemistry
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doi:10.1016/j.ejmech.2008.08.004
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journal_title:European journal of medicinal chemistry
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doi:10.1016/j.ejmech.2020.112367
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2011.12.030
更新日期:2012-03-01 00:00:00
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/j.ejmech.2013.11.029
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2013-08-01 00:00:00
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.03.022
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2013.09.038
更新日期:2013-11-01 00:00:00
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
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更新日期:2009-06-01 00:00:00
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2009.10.032
更新日期:2010-02-01 00:00:00
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2008.01.036
更新日期:2008-12-01 00:00:00
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2010.07.007
更新日期:2010-10-01 00:00:00
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journal_title:European journal of medicinal chemistry
pub_type: 更正并重新发布的文章,杂志文章
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更新日期:2004-10-01 00:00:00
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journal_title:European journal of medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.ejmech.2015.07.002
更新日期:2015-08-28 00:00:00