Joong-jae LEE, Hyun Jung KIM, Jae-Min YUK, Hae-Kap CHEONG, Eun-Kyeong JO, Hak-Sung KIM
언어
영어(ENG)
URL
https://www.earticle.net/Article/A174341
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원문정보
초록
영어
Variable lymphocyte receptors (VLRs) which are leucine-rich repeat (LRR) proteins play important roles in adaptive immunity of jawless vertebrates such as lamprey and hagfish that lack Ig-based immune system. The VLRs are also the oldest immune receptors and the only non-Ig scaffold used for antigen recognition in nature. Based on their modularity and antigen binding property, we have successfully designed a engineered VLR scaffold protein, Repebody, with high physicochemical stability and mass productivity in prokaryote expression system. In order to verify whether Repebody acts as a universal molecular binder, we carried out the directed evolution of Repebody by saturation mutagenesis of concave surface and phage display technology for selection of ligand binders. The resulting binder D3 exhibits the nanomolar binding affinity for Interleukin-6 with target specificity. For general and practical applications, we further designed repeat module- based approach for affinity maturation of Repebody. Through the method, high affinity binders were successfully isolated from additional module library and the best clone D3E8C4 exhibits about 50-fold binding affinity improvement with a dissociation constant (KD) of 397pM, and which shows inhibition of IL-6 activity in human monocyte at low doses (0.1ug/ml). These results suggest that Repebody acts as not only an alternative scaffold but also a potential therapeutic agent as the artificial antibody and that module-based engineering method is effective for library design and affinity maturation of repeat proteins.
한국생물공학회 [The Korean Society for Biotechnology and Bioengineering]
설립연도
1984
분야
공학>생물공학
소개
이 법인은 생물 공학의 발전과 보급에 이바지하고, 회원 상호 간의 연구 협력과 친목을 도모함을 목적으로 한다
1. 생물공학 분야의 발전을 위한 연구 협력
2. 생물공학의 실용화를 촉진시키기 위한 산학 협동
3. 학술연구 발표회, 강연회, 연수회 등 학술활동의 개최
4. 국,영문 학술지,소식지,학술회의 Proceedings 및 학술도서의 발간
5. 생물공학 발전을 위한 정책 건의
6. 기타 국제 교류 등 본 학회의 목적 달성을 위한 제반 활동