2-CTC 수지를 이용한 효과적인 펩타이드-퍼릴렌의 합성 및 광역학치료로의 응용

학위논문 (석사)-- 서울대학교 대학원 공과대학 화학생물공학부, 2017. 8. 이윤식.Perylene-3,4,9,10-tetra carboxylic diimide (PDI) has remarkable features as a photosensitizer in Photodynamic Therapy. However, PDIs poor solubility in aqueous condition limits its use. So it is commonly functionalized by various substituents on imide positions where two nitrogen groups comprised with imide moiety. However, there has been a technical limitation to conjugate them with proper amine gorups such as amino acids or peptides having pi-electron system. To overcome this problem, solid-phase peptide synthesis (SPPS) method has been utilized to conjugate peptides having diverse pi-electron functional molecules. But still other problems appeared such as low yield with harsh reaction condition. Therefore, a new method was designed to overcome such disadvantages of conventional SPPS method. For this, reaction times, loading level, and solvent system were optimized. In this research, RGD sequence was conjugated as a substituent on imide position. The RGD sequence is well known as a cell attachment component. Thus, we could develope very useful materials which has both strong cell adhesion ability and photosensitizer for photodynamic therapy.1. Introduction 1 1. 1 Perylene-3,4,9,10-tetra carboxylic diimide 1 1. 2 Peptide-conjugated pi-electron material 3 1. 3 Peptide-conjugated PDI for photodynamic therapy 7 1. 4 Research Objective 11 2. Experimental Section 12 2. 1 General 12 2. 2 Synthesis of L-alanine conjugated perylene dimide (PDI-[A]2) 14 2. 3 Synthesis of PDI-[ARGD]2 by SPPS method 15 2. 4 Reverse phase silica gel column chromatography 17 2. 5 Cell Preparation 18 2. 6 Cell viability test 19 2. 7 Photodynamic Therapy using PDI-[ARGD]2 and PDI-[A]2 20 3. Results and discussion 21 3. 1 Synthesis of PDI-[A]2 21 3. 2 Synthesis and characterization of PDI-[ARGD]2 23 3. 3 Optical properties of PDI-[ARGD]2 29 3. 4 Cell toxicity test of PDI-[ARGD]2 on 3T3 cells 31 3. 5 Fluorescence image of 3T3 cell line 34 3. 6 Photodynamic Therapy with PDI-[ARGD]2 36 4. Conclusion 38 5. References 39 Appendix 42 6. Abstract in Korea 44Maste