含萘二甲醯亞胺之具生物功能奈米纖維及超分子水凝膠

Abstract

經由競爭黏層和突變實驗，細胞外基質中含有的胜肽序列逐漸被發現。我們合成一系列以萘二甲醯亞胺為基底且包含 DGEA、IKVAV、GFF及FFG的新穎水凝膠。本文將分成三個部分來探討，第一部分為合成包含DGEA胜肽序列的超分子水凝膠。DGEA胜肽序列在第一型膠原蛋白上已被辨認出對21整聯蛋白受器具有專一性，我們進一步比較不同細胞株的生物相容性及測試NO2-NI及衍生物一系列的生物測試去了解是否原本具有生物毒性的發光團會因解結合胜肽序列而降低其生物毒性。超分子水凝膠因子會因為連接不同的發光團1,8-Naphthalimide-N-acetic acid 或是4-Nitro-1,8-Naphthalimide-N-acetic acid而有不同的螢光特性。第二章則是有關 IKVAV 胜肽序列之水凝膠合成。IKVAV序列為位於α-1鏈負責細胞粘附和神經突增生的層粘連蛋白。基於原子經濟學和綠色化學，我們減少了合成水凝膠因子的分子數量形成可自組裝含有生物活性超分子水凝膠。最後一章則有關於超分子水凝膠中含FF胜肽序列的生物相容性探討。

Adhesive peptide sequences within many ECM proteins have been discovered via competitive adhesion assays and mutagenesis experiment. In our laboratory, Novel hydrogels based on Naphthalimide with peptide sequences DGEA, IKVAV, GFF, and FFG have been synthesized. This thesis has three-fold. In the first part, DGEA-containing peptides hydrogelators based on naphthalimide are developed. The DGEA tetra-peptide sequence is the shortest collagen type I-derived motif recognized by the collagen-binding integrin 21. Also, the materials have significant differences in their fluorescence intensity because of the capping group, 1,8-Naphthalimide-N-acetic acid and 4-Nitro-1,8-Naphthalimide-N-acetic acid. In the second part, small molecule hydrogels containing IKVAV polypeptide induced self-assembly to form nanofiber gel was synthesized. The IKVAV peptide sequence is located in the α-1 chain of laminin responsible for cell adhesion and neurite outgrowth. We reduce the molecular weight of IKVAV-containing hydrogelator and toward a better material that fits the Atomic economy and Green chemistry. In the last one, we capped peptide sequences, GFF and FFG with aromatic group, naphthalimide, and compared the cell viability of NI-GFF and NI-FFG. We also tested the cell viability of 4-Nitro-1,8-naphthalimide, NO2-FDGEA and NO2-FIKVAV to know whether if the cytotoxicity of the materials can be improved by conjugating the peptide sequences.