Self-Assembly Of Borono-Peptides And Their Biomedical Applications

Recently, peptide-based stimuli-responsive self-assembling biomaterials have attracted particular attentions and activities. Rationally designed peptide building blocks can be triggered to self-assemble into various soft materials such as three dimensional hydrogels and membranes, which involve a series of supramolecular architectures including fibers, tubes, ribbons and spheres, showing great potential applications in3D cell culture, tissue engineering, drug/gene delivery and bio-sensing. Based on the numerous researches of peptide-based stimuli-responsive self-assembly and receptor-ligand relevant stimuli-responsive manner, here, we designed and fabricated a series of borono-peptides, systematically studied their self-assembly behaviors and elicited their biomedical applications.Chapter1reviewed the recent progress in peptide-based stimuli-responsive self-assemblies and their biomedical applications. Originated from the special correlation between chemical structures/conformations and self-assembly behaviors, various stimuli-responsive manners were exploited to regulate the molecular structures/conformations of the rationally designed peptide building blocks, aiming to trigger the transformations in morphologies and functions for specific biomedical applications.In Chapter2, a series of structural complementary borono-decapeptides (BPs1-3) were designed and synthesized for supramolecular self-assembly. After dissolving these borono-decapeptides in deionized (DI) water, well-defined nanofibers were formed in BP1(B(OH)2VEKELVKEKL-OH) and BP3(B(OH)2AELELARARL-OH) solutions. It was found that the self-assembled borono-decapeptide BP1and BP3have a parallel (3-sheet conformation in the formed nanofibers. The strategy demonstrated here shows a great prospect in preparation of well-ordered nanofibers and hydrogels via rationally designing the peptide molecule structures. In Chapter3, a unique peptide nanofibrous indicator (NFI) was fabricated based upon the binding and self-assembly between a borono-peptide(BP) and alizarin red S (ARS). NFI exhibited an intense response to sialyl Lewis X (sLex) tetrasaccharide, which is over-expressed in human hepatocellular carcinoma (HCC) cell lines. Importantly, this NFI presented the specifically recognizing capability to HepG2cells through eye-detectable color change resulting from stronger binding induced displacement. This novel technique for cancer cell identification through direct unaided-eye judgment will open up an innovative platform for cancer cell detection.In Chapter4, three arginine-containing borono-peptides (BPsl-3) were designed and synthesized. BPsl-3could spontaneously self-assemble into supramolecular architectures at a physiological environment. Alizarin red S (ARS), responsible for specific recognition towards BPs to form five-membered ring borate esters (ARS/BPs) with drastic changes in fluorescent feature and visible color, was employed to regulate the self-assembly of BPs. It was found that ARS/BPs complex can be rapidly formed from the judgment of color change and further regulate the self-assembly into more ordered and sophisticated supramolecular architectures.In Chapter5, three borono-peptides (BPs1-3) were designed and synthesized. Based on the specific receptor-ligand recognition interaction between diol and phenylboronic acid moiety and the formation of boronic ester compound, two polyhydric phenols (2,3-Naphthalenediol:NDO; triphenylene-2,3,6,7,10,11-hexaol: HHTP) were employed to regulate the self-assembly of these borono-peptides. Following the formation of π-conjugated unitary and ternary boronic ester compound, the supramolecular architectures subsequently transformed into new well-ordered nanostructures, accomplishing the π-conjugation regulated template self-assembly. This strategy demonstrated here shows a promising in intracellular self-assembly for reconstruction of cellular microenvironments and regulation of cell functions.