LEE, REIKO TAKASAKA,李 玲子,李 玲子,LEE, YUAN-CHUAN,李远川,李遠川,WANG, MEI HUI,王美惠,王美惠,LIN, WUU JYH,林武智,林武智
申请号：
TW099132657
公开号：
TWI458493B
申请日:
2010.09.27
申请国别(地区):
TW
年份:
2014
代理人:
摘要：
This invention provides novel liver targeting agents and their synthetic methods. Liver targeting agent, with a lysine based nitrilo triacetic acid structure as backbone which acquires multivalency with saccharide groups, to bind with a galactosamine chain or lactose chain. In particular, only one amino acid L-lysine is involved to provide trivalency. All carboxyl group in Nε-benzyloxycarbonyl-Nα- dicarboxymethyl-L-lysine can be conjugated with three glycosides of ahGalNAc or ahLac in one step. This invention also provides a hexa-lactoside. In particular, the TFA-AHA-Asp was used to conjugate 2 moles of NTA(ahLac)3. This invention also provides a method for adding spacer between NTA (nitrilo-triacetic acid) and DTPA (diethylene tetraamine penta acetic acid). The extended hepatocyte-specific glyco-ligand has higher111In-radiolabelling yield than those non-extended.本發明提供了新穎肝標靶藥劑和合成方法。特別是此肝標靶藥劑結構是以帶有離胺酸(lysine)之硝基三醋酸(nitrilo-triacetic acid,NTA)為骨架來和半乳胺醣鏈或乳醣鏈鍵結而成。其中,只需一種胺基酸-“離胺酸”-即可提供三價的結構,以ε-苯甲氧羰基-N,N-二羧甲基-左旋離胺酸(ε-benzyloxycarbonyl-N,N-bis(carboxymethyl)-L-lysine)中的任何羧基皆可與6-胺己基β-N-乙醯基半乳胺醣(6-aminohexyl β-N-acetylgalactosamine)結合成三鏈聚合糖苷。另外本發明也可提供六鏈聚合糖苷;以及本發明也提供Nα-(三氟乙醯胺基己醯基)-左旋天門冬胺酸(Nα-(trifluoroacetaminohexanoyl)-aspartic acid)與2個分子之硝基三醋酸(三鏈-6-胺己基乳醣苷)的鍵結方法;此外,本發明亦提供於硝基三醋酸與二伸乙基四胺五乙酸(DTPA)間增長臂之方法,此方法有助於提升肝細胞專一醣配體在標誌放射性同位素之放射化學產率。
