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Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo

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dc.contributor.author박병우-
dc.date.accessioned2019-11-11T05:21:49Z-
dc.date.available2019-11-11T05:21:49Z-
dc.date.issued2000-
dc.identifier.issn1087-0156-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/171810-
dc.description.abstractMonoclonal antibodies specific for the p185HER2/neu growth factor receptor represent a significant advance in receptor-based therapy for p185HER2/neu-expressing human cancers. We have used a structure-based approach to develop a small (1.5 kDa) exocyclic anti-HER2/neu peptide mimic (AHNP) functionally similar to an anti-p185HER2/neu monoclonal antibody, 4D5 (Herceptin). The AHNP mimetic specifically binds to p185HER2/neu with high affinity (KD=300 nM). This results in inhibition of proliferation of p185HER2/neu-overexpressing tumor cells, and inhibition of colony formation in vitro and growth of p185HER2/neu-expressing tumors in athymic mice. In addition, the mimetic sensitizes the tumor cells to apoptosis when used in conjunction with ionizing radiation or chemotherapeutic agents. A comparison of the molar quantities of the Herceptin antibody and the AHNP mimetic required for inhibiting cell growth and anchorage-independent growth showed generally similar activities. The structure-based derivation of the AHNP represents a novel strategy for the design of receptor-specific tumor therapies.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherNature America Publishing-
dc.relation.isPartOfNature Biotechnology-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHAntibodies, Monoclonal/chemistry*-
dc.subject.MESHAntibodies, Monoclonal/pharmacology*-
dc.subject.MESHAntibodies, Monoclonal/therapeutic use-
dc.subject.MESHAntibodies, Monoclonal, Humanized-
dc.subject.MESHAntineoplastic Agents/chemistry*-
dc.subject.MESHApoptosis-
dc.subject.MESHAstrocytoma-
dc.subject.MESHBiosensing Techniques-
dc.subject.MESHDoxorubicin/therapeutic use-
dc.subject.MESHDrug Design-
dc.subject.MESHDrug Therapy, Combination-
dc.subject.MESHGamma Rays-
dc.subject.MESHMice-
dc.subject.MESHMice, Nude-
dc.subject.MESHMolecular Mimicry*-
dc.subject.MESHProtein Binding-
dc.subject.MESHRadiotherapy, Adjuvant-
dc.subject.MESHReceptor, ErbB-2/antagonists & inhibitors*-
dc.subject.MESHTrastuzumab-
dc.subject.MESHTumor Cells, Cultured/drug effects-
dc.subject.MESHTumor Cells, Cultured/radiation effects-
dc.titleRationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Surgery (외과학교실)-
dc.contributor.googleauthorByeong-Woo Park-
dc.contributor.googleauthorHong-Tao Zhang-
dc.contributor.googleauthorChuanjin Wu-
dc.contributor.googleauthorAlan Berezov-
dc.contributor.googleauthorXin Zhang-
dc.contributor.googleauthorRaj Dua-
dc.contributor.googleauthorQiang Wang-
dc.contributor.googleauthorGary Kao-
dc.contributor.googleauthorDonald M. O'Rourke-
dc.contributor.googleauthorMark I. Greene-
dc.contributor.googleauthorRamachandran Murali-
dc.identifier.doi10.1038/72651-
dc.contributor.localIdA01475-
dc.relation.journalcodeJ02290-
dc.identifier.eissn1546-1696-
dc.identifier.pmid10657127-
dc.identifier.urlhttp://www.nature.com/articles/nbt0200_194-
dc.contributor.alternativeNamePark, Byeong Woo-
dc.contributor.affiliatedAuthor박병우-
dc.citation.volume18-
dc.citation.number2-
dc.citation.startPage194-
dc.citation.endPage198-
dc.identifier.bibliographicCitationNature Biotechnology, Vol.18(2) : 194-198, 2000-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers

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