• 제목/요약/키워드: ANG-2

검색결과 4,981건 처리시간 0.043초

Angiogenesis Inhibitor Derived from Angiostatin Active Sites

  • Park, Kyoung-Soo;Lim, Dong-Yeol;Park, Sang-Don;Kim, Min-Young;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • 제25권9호
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    • pp.1331-1335
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    • 2004

  • Angiogenesis is essential for the growth and persistence of solid tumors. Their metastases, anti-angiogenesis could lead to the suppression of tumor growth. One of the main strategies of cancer treatment is developing molecules of anti-angiogenic activity. In this study, two angiogenic inhibitors, Ang3 (KLFDF) and Ang4 (XLFDF) derived from KLYDY, which is the sequence of angiostatin active sites kringle 5, were designed and synthesized. Previously we reported the activities and structures of two inhibitors, Ang1 (KLYDY) and Ang2 (KLWDF). In order to investigate the effect of Phe substitution, Ang3 was designed with a sequence of KLFDF. In order to reduce conformational flexibility of side chain in Lys, Ang4 was designed with a sequence of XLFDF, where X has amino substituted phenyl ring. Solution structures of those inhibitors were investigated using NMR spectroscopy and their activities as angiogenesis inhibitors were studied. Ang1 and Ang2 show angiogenic activities, while Ang3 and Ang4 have no activities and have extended structures compared to Ang1 and Ang2. Therefore, Phe rings do not have effective hydrophobic interactions with other aromatic residues in Ang3 and Ang4. The representative structure of Ang2 has a stable intramolecular hydrogen bond. Therefore, intramolecular hydrogen bonding might be more important in stabilizing the structure than the hydrophobic interactions in these inhibitors. More rigid structure, which can be expected to have higher activities and better match with the receptor bound conformations, can be obtained with a constrained cyclic structure. Further peptidomimetic approaches should be tried to develop angiogenesis inhibitors.

  • https://doi.org/10.5012/bkcs.2004.25.9.1331 인용 PDF KSCI

Hydrogen Peroxide Activates ERK in Cultured Feline Ileal Smooth Muscle Cells

  • Song, Hyun-Ju;Lee, Tai-Sang;Jeong, Ji-Hoon;Park, Joon-Hong;Choi, Tae-Sik;Lee, Doo-Won;Sohn, Uy-Dong
    • 대한약학회:학술대회논문집
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    • 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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    • pp.242.1-242.1
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    • 2002

  • H$_2$O$_2$ has been shown to act as a signaling molecule involved in many cellular functions such as oxidant-induced stress, apoptosis, proliferation. In this study, we investigated the action mechanisms of H$_2$O$_2$ on activation of Extracellular Signal-Regulated Protein Kinase(ERK) in cultured feline ileal smooth muscle cells(ISMC). Western blot analysis done with phospho-specific MAP kinases antibodies demonstrated that potent activation of ERK and moderate activation of SAPK/JNK occurred within 30 min of H$_2$O$_2$ treatment. (omitted)

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