Design, synthesis and characterization of peptidomimetic conjugate of BODIPY targeting HER2 protein extracellular domain.


: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.


Eur J Med Chem


Banappagari S,McCall A,Fontenot K,Vicente MG,Gujar A,Satyanarayanajois S




Has Abstract


2013-07-01 00:00:00












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    pub_type: 杂志文章


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    pub_type: 更正并重新发布的文章,杂志文章


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    authors: Galal SA,Hegab KH,Kassab AS,Rodriguez ML,Kerwin SM,el-Khamry AM,el-Diwani HI

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    authors: Ibáñez E,Plano D,Font M,Calvo A,Prior C,Palop JA,Sanmartín C

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    authors: Liechti C,Séquin U,Bold G,Furet P,Meyer T,Traxler P

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    authors: Emirdağ-Öztürk S,Karayıldırım T,Çapcı-Karagöz A,Alankuş-Çalışkan Ö,Özmen A,Poyrazoğlu-Çoban E

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    authors: Hilal HS,Ali-Shtayeh MS,Arafat R,Al-Tel T,Voelter W,Barakat A

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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Šmelcerović A,Tomović K,Šmelcerović Ž,Petronijević Ž,Kocić G,Tomašič T,Jakopin Ž,Anderluh M

    更新日期:2017-07-28 00:00:00

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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Metwally K,Pratsinis H,Kletsas D

    更新日期:2017-06-16 00:00:00

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    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Pinto B,Caciagli F,Riccio E,Reali D,Sarić A,Balog T,Likić S,Scarpato R

    更新日期:2010-09-01 00:00:00

  • Novel semicarbazides and ureas of primaquine with bulky aryl or hydroxyalkyl substituents: synthesis, cytostatic and antioxidative activity.

    abstract::Novel primaquine semicarbazides 7a-l and ureas 9a-g with modified benzhydryl, trityl, phenyl or hydroxyalkyl substituents were prepared and evaluated for cytostatic and antioxidative activities. Two synthetic approaches for preparation of the title semicarbazides were applied, both having certain advantages. In the fi...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Pavić K,Perković I,Cindrić M,Pranjić M,Martin-Kleiner I,Kralj M,Schols D,Hadjipavlou-Litina D,Katsori AM,Zorc B

    更新日期:2014-10-30 00:00:00

  • Improved synthesis and comparative analysis of the tool properties of new and existing D-ring modified (S)-blebbistatin analogs.

    abstract::(S)-Blebbistatin is a widely used research tool to study myosin II, an important regulator of many motility based diseases. Its potency is too low to be of clinical relevance, but identification of analogs with enhanced potency could deliver leads for targeted pharmacotherapeutics. This, however, requires a profound i...

    journal_title:European journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Verhasselt S,Roman BI,Bracke ME,Stevens CV

    更新日期:2017-08-18 00:00:00