Please use this identifier to cite or link to this item:
|Title:||Design and synthesis of cysteine-rich peptides||Authors:||Qiu, Yibo||Keywords:||DRNTU::Science::Biological sciences::Biochemistry||Issue Date:||2014||Source:||Qiu, Y. (2016). Design and synthesis of cysteine-rich peptides. Doctoral thesis, Nanyang Technological University, Singapore.||Abstract:||My thesis focuses on the methodology and application of novel synthetic strategies for high-throughput preparation of the cyclic cysteine-rich peptides with therapeutic potential. Cyclic cysteine-rich peptides are macrocyclic peptides with intramolecular disulfide bonds. The end-to-end cyclic backbone together with multiple disulfide bonds provides conformational constraints to enhance the structural stability. My strategy involves synthesizing these peptides by chemical approaches using solid-phase peptide synthesis. A new cyclization method was developed employing an N-S acyl shift mechanism to mimic the natural production of peptide bonds. The oxidative folding process is also optimized by introducing organic solvents. With the novel cyclization and the organic folding strategy in a one-pot manner, I have successfully prepared cyclic cysteine-rich peptides in a shorter reaction time with an improved yield than with conventional methods. They could be used as a simple and high-throughput synthetic platform to prepare cyclic cysteine-rich peptides. In addition, the substrate specificity of a novel transpeptidase named butelase 1 was also investigated for ligation and cyclization reactions. With high efficiency and broad substrate specificity, it would be exploited as a novel chemoselective approach for peptide and protein engineering. For applications, the cyclic peptide sunflower trypsin inhibitor-1 which possesses a cyclic backbone is modified by a grafting approach with bioactive peptides while retaining the cyclic peptide scaffold. New analogs with improved stability and new functions were developed as a proof-of-concept to advance the development of potential peptide biologics.||URI:||https://hdl.handle.net/10356/62189||DOI:||10.32657/10356/62189||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Theses|
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.