2012 Fiscal Year Final Research Report

Development of Fab molecule with the stable scaffold for next generation

Research Project

Project/Area Number	23655160
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Chemistry related to living body
Research Institution	Kyushu University
Principal Investigator	UEDA Tadashi 九州大学, 薬学研究院, 教授 (90184928)
Co-Investigator(Kenkyū-buntansha)	SHIROISHI Mitsunori 九州大学, 薬学研究院, 助教 (00380527)
Co-Investigator(Renkei-kenkyūsha)	ABE Yoshito 九州大学, 薬学研究院, 准教授 (60315091)
Project Period (FY)	2011 – 2012
Keywords	抗体工学 / 安定化 / アミノ酸改変 / ヒト型Fab / 蛋白質の劣化
Research Abstract	In order to prepare humanized Fab with the stable scaffold for next generation, we tried to stabilize the constant region of humanized Fab. At first, we showed that Asn138 in L chain of the Fab was easy to deamidate to Asp of Asn residues in the Fab. After preparation of the Fab mutants where Asn138 is mutated to Asp or Ala in L chain of the Fab, respectively, we examined their stabilities against guanidine hydrochloride at pH 6.5 and 25℃. As a result, we found that Asp138Fab was more destabilized than the nonmutant Fab while Ala138Fab had a stability similar to the nonmutant Fab. After heating at pH 9, the residual amount of Ala138Fab was higher than that of the nonmutant Fab.

(1 results)