Sialic acid-binding immunoglobulin-like lectin (Siglec) 7 is one of the sialic acid binding protein that plays an important role in immune system. Siglec 7 is expressed on natural killer cells and displays a unique ligand binding properties comparing to the other members of the Siglec family, specifically binds to 2,8-disialyl residues. The precise structural analysis of Siglec 7 has been already performed, and amino acid residues involved in the ligand binding are reported. In such context, we set out the first total chemical synthesis of Siglec 7 carbohydrate binding domain (CBD) which consists of 127 amino acid residues. Since chemical synthesis can easily introduce unnatural amino acids, we envisioned that we could produce an artificial sialic acid binding lectin based on this chemical synthetic strategy. The synthesis of Siglec 7 CBD was carried out by convergent total chemical synthesis. The whole polypeptide was assembled from 5 peptide segments (Figure), which were synthesized by conventional solid phase peptide synthesis. We applied native chemical ligation (NCL) for the coupling of these segments sequentially from C-terminus, combined with alkylation with haloacetoamide or desulfuration reaction. These reactions can provide pseudo-Gln residue or Ala residue from Cys residues at the ligation sites. Based on these strategies we have successfully obtained the full-length polypeptide of Siglec 7 CBD and currently are investigating the in vitro folding step.
저자
Akihisa Otsuki [ Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043 Japan ]
Ryo Okamoto [ Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043 Japan ]
Masayuki Izumi [ Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043 Japan ]
Yasuhiro Kajihara [ Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka, 560-0043 Japan ]
본 학회는 화학, 생화학, 분자생물학, 미생물학, 식품공학, 의학, 약학, 유전공학 및 생물공학, 환경 및 기타 공업 등 전 분야의 탄수화물관련 이론과 기술을 연구 발전시키고 산학협동을 통해 이를 보급하여 국내 관련 산업의 발전 및 국민생활의 과학화에 기여하고자 하며, 이러한 목표와 비젼의 실현을 위해 회원들이 적극적인 참여와 활동을 전개하고자 한다.