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本論文中我們將介紹一種新穎且便利的利用微波的固相多肽合成方法，以及在此方法協助下對一組混合肽之間相互作用的研究。與傳統的多肽合成相比，微波輻射幫助提高耦合過程的效率，從而大大縮短了合成時間，以及提高了反應效率。家庭用和實驗室用微波爐的比較表明，家用微波爐在實驗室條件下足以勝任微波輔助固相多肽合成。在第二部分，我們利用微波固相多肽合成合成了一組多肽用以探究其之間相互作用。一對在之前文獻報導的，通過庫篩選得到的結合肽被用來與另一組捲曲肽組合構成混合肽，期望得到強而且具特異性的相互作用以用作蛋白的標記。然而文獻報導的這對多肽並未達到預期的相互作用，因此我們需要在後續實驗中重新設計混合肽。 / This thesis summarizes an investigation into a novel solid-phase peptide synthesis protocol assisted by microwave irradiation, as well as an attempt to design hybrid peptides for enhanced binding properties. Compared with conventional peptide synthesis, a brief microwave irradiation during coupling and deprotection was shown to significantly reduce the time for peptide synthesis, at the same time yielding satisfactory product purity. A comparison of a domestic and a laboratory microwave oven indicated that the former could be easily adapted for conducting microwave-assisted solid phase peptide synthesis in a research laboratory, a facile and budget-efficient solution for enhanced efficiency in solid phase synthesis. In the second part of the research, we utilized the developed protocol to synthesize a set of peptides to investigate peptide-peptide interaction. A pair of binding peptides previously identified through library screening and genetic selection reported in literature was fused with designed coiled coil peptides to afford hybrid peptides, which was expected to result in exceptionally strong interaction and enhanced specificity. These hybrid peptide pairs could find applications in protein labeling, immunoblotting, and purification. However, the peptide pair did not demonstrate the claimed binding affinity in the literature. Therefore, the current design is flawed, and we shall re-design hybrid peptides based on other binding pairs in the following research. / Detailed summary in vernacular field only. / Zhang, Han. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references. / Abstracts also in Chinese. / 摘要 --- p.I / ABSTRACT --- p.II / TABLE OF CONTENTS --- p.III / ACKNOWLEDGEMENT --- p.V / ABBREVIATION --- p.VI / Chapter Chapter 1 --- Microwave -assisted synthesis of a defensin peptide: a comparison of domestic and laboratory microwaves --- p.1 / Chapter 1. --- INTRODUCTION --- p.1 / Chapter 1.1. --- Defensins --- p.1 / Chapter 1.2. --- Solid-phase peptide synthesis (SPPS) --- p.5 / Chapter 1.3. --- Microwave (MW) heating in organic synthesis --- p.6 / Chapter 1.4. --- Microwave (MW) heating assisted solid phase peptide synthesis --- p.7 / Chapter 2. --- METHODS --- p.8 / Chapter 2.1. --- General synthetic approach of SPPS --- p.8 / Chapter 2.2. --- Microwave-assisted SPPS --- p.9 / Chapter 2.3. --- Analysis and characterization of the product --- p.12 / Chapter 3. --- RESULT AND DISCUSSION --- p.12 / Chapter 3.1. --- Exploring the coupling step under microwaving --- p.12 / Chapter 3.2. --- Nαdeprotection under microwave heating --- p.14 / Chapter 3.3. --- Synthesis of the target peptide --- p.16 / Chapter 3.4. --- SPPS in laboratory MW reactor --- p.18 / Chapter 3.5. --- SPPS by standard conventional method --- p.20 / Chapter 3.6. --- Comparison of the three methods --- p.21 / Chapter 3.6.1. --- Product p Product p urity --- p.21 / Chapter 3.6.2. --- Time and cost --- p.24 / Chapter 3.6.3 --- Sc alabiltiy of SPPS --- p.24 / Chapter 4. --- Exploration of the mechanism of microwave-assisted SPPS: thermal or nonthermal effect? --- p.25 / Chapter 5. --- CONCLUSION --- p.29 / REFERENCE --- p.30 / Chapter Chapter 2 --- Hybrid peptides with enhanced affinity and specificity for protein labeling --- p.33 / Chapter 1. --- INTRODUCTION --- p.33 / Chapter 1.1. --- Protein labeling --- p.33 / Chapter 1.2. --- Hybrid peptides sequences --- p.35 / Chapter 2. --- EXPERIMENTAL SECTION --- p.36 / Chapter 2.1. --- HPLC result --- p.37 / REFERENCE --- p.48

Thesis (Ph.D.) - University of Queensland, 2003. / Includes bibliography.

Peptides are short, sequence and length specific oligomers composed of small amino acid residues. Nature has refined these peptide sequences and their endogenous function through evolution. In addition, peptides have played an important role in medicine, which has lead to further research into developing peptides as lead pharmaceuticals (therapeutic peptides). Unfortunately, therapeutic peptides are inferior as drug candidates due to their low oral bioavailability; immunogenicity and potential to be attacked by peptidases. Fortunately, peptides can be modified by steric constraints, cyclization, and/or replacement of the peptide backbone itself creating a mimic (peptidomimetic) of the original peptide. Peptidomimetics are deliberately designed to have increased protease resistance, reduced immunogenicity and improved bioavailability when compared to the original endogenous peptide. One such peptide, Magainin is a O One such peptide, Magainin is a well-studied, a-helical peptide found in African clawed frogs. This peptide has antibiotic properties (against pathogenic bacteria), which partly arises from the hydrophilic portion of the peptide having basic amino acid side chains periodically disposed on one side of the a-helix. This property of magainin causes its attraction to negatively charged bacteria cell membranes. Unfortunately, as in the case of other antibiotics, pathogenic bacteria have developed effective countermeasures against magainin. We designed a peptidomimetic based on magainin and implemented a plan to determine what type of molecules could be assembled for a magainin mimic. We successfully utilized molecular modeling (Monte Carlo conformational search), as well as results from previous experiments to elucidate what type of molecules, as well as how many molecules would be necessary to create a novel helical-like magainin peptidomimetic. It was discovered that C2 symmetric diamines would be best at generating the helical-like motif and the amino acid lysine to generate the basic side chain. The next step was the successful connection of two C2 symmetric molecules via a urea linkage and then one more connection to a lysine (a-amino group) residue, creating a short sequence of oligoureas (trimers). Finally, attempts to connect the oligoureas trimers were attempted using a solid-phase synthesis approach to generate a functional magainin mimic.

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