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Single-Shot Solid-Phase Synthesis of Full-Length H2 Relaxin Disulfide Surrogates |
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| Authors: | Rui Zhao Pan Shi Ji-bin Cui Chaowei Shi Xiao-Xiong Wei Jie Luo Zhemin Xia Wei-Wei Shi Yingxin Zhou Jiahui Tang Changlin Tian Mark Meininghaus Donald Bierer Jing Shi Yi-Ming Li Lei Liu |
| Institution: | 1. Department of Chemistry, Center for BioAnalytical Chemistry, Hefei National Laboratory of Physical Science at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 China
School of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei, 230009 China These authors contributed equally to this work.;2. Department of Chemistry, Center for BioAnalytical Chemistry, Hefei National Laboratory of Physical Science at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 China These authors contributed equally to this work.;3. School of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei, 230009 China These authors contributed equally to this work.;4. Department of Chemistry, Center for BioAnalytical Chemistry, Hefei National Laboratory of Physical Science at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 China;5. School of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei, 230009 China;6. Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing, 100084 China;7. Drug Discovery Sciences, Bayer AG, Pharmaceuticals, Aprather Weg 18?A, 42096 Wuppertal, Germany |
| Abstract: | Chemical synthesis of insulin superfamily proteins (ISPs) has recently been widely studied to develop next-generation drugs. Separate synthesis of multiple peptide fragments and tedious chain-to-chain folding are usually encountered in these studies, limiting accessibility to ISP derivatives. Here we report the finding that insulin superfamily proteins (e.g. H2 relaxin, insulin itself, and H3 relaxin) incorporating a pre-made diaminodiacid bridge at A-B chain terminal disulfide can be easily and rapidly synthesized by a single-shot automated solid-phase synthesis and expedient one-step folding. Our new H2 relaxin analogues exhibit almost identical structures and activities when compared to their natural counterparts. This new synthetic strategy will expediate production of new ISP analogues for pharmaceutical studies. |
| Keywords: | Chemical Protein Synthesis Diaminodiacid H2 Relaxin Disulfide Surrogates Insulin Superfamily Proteins |