Peptide Beacon,Supramolecular Aggregation And Supramolecular Chirality Study Based On N-Amidothioureas

Peptide is abundant in secondary structures and serves as the most important basic substance of life.The formation and stability of peptide secondary structure have close relationship with protein folding and vital activity regulation.Among the various studies about peptide secondary structures,?-sheet structures get increasing attention.As an important component of ?-sheet,?-turn orientates the peptide chains and provides basic structure for the formation and stability of ?-sheet,which plays a critical role in diseases related protein aggregation.?-Turn also constitutes binding epitopes in protein-protein interaction and protein-nucleic acid recognition,so that they can be used in the design of recognition scaffolds and novel medicines.?-Turn as the structural motif leads to the conformation change,which not only facilitates the host-guest recognition and signal response,but also sterically connects the different parts of the molecule,inducing supramolecular chirality.Supramolecular chirality plays a leading role in the formation of helical polymers,and provides a new hint to understand chiral amplification,chiral selectivity and the origin of homochiraiity.Our group has established N-amidothiourea as an excellent ?-turn template for its helical structure and properties,making it convenient for ?-turn applications.In this dissertation,N-amidothiourea is employed as the structure basis,modified with fluorophores,hydrophobic groups and binding site,respectively,to construct peptide based N-amidothioureas for anion recognition,building helical polymers and expression of supramolecular chirality.The dissertation consists of four chapters.In Chapter 1,?-turn and its applications are introduced at first,followed by research progress of the ?-turn structure in N-amidothioureas.Next,progress in peptide beacon,supramolecular polymer and its chirality feature are reviewed.At last the objectives of this dissertation are presented.In chapter 2,peptide beacons,Phel and Phe3,based on N-amidothiourea and control molecules Phe2 and Phe4 with no ?-turn structure are designed and synthesized.Peptide beacons contain the ten-membered ring intramolecular hydrogen bond(?-turn)with thiourea moiety acting as the binding site.The distance-dependent exciplex or excimer formation and the respective dual emission are expected to undergo changes upon binding of the model anions to the thiourea moiety designed to locate within the turn structure;that leads to a conformational change.Whereas the control molecules do not behave like peptide beacon because of the absence of ?-turn,exhibiting the much lower sensitivity to anion.Phenylalanine residue in Phel is replaced by other amino acid residues to establish the generality of this kind of peptide beacon,from which it is found that a stronger hydrogen bond in the ?-turn affords more sensitive response to anion.Chapter 3 develops the helical supramolecular po lymer based on pyrenyl-substituted N-amidothioureas.By comparing the aggregation behavior of pyrenyl-substituted N-amidothioureas of similar structure,it was made obvious that molecules bearing ?-turn aggregate,forming helical polymers,whereas molecules without ?-turn structure are unable to aggregate.Although the aggregation capability of the non-?-turn structured molecules can be enhanced by surfactant,its rate of aggregation and the stability of the aggregates remain worse than ?-turn structured molecule.Traces of ?-turn structured molecule can induce the aggregation of the non-?-turn structured molecule,which highlights the critical role of the ?-turn structure in polymerization.This property offers insights into the regulation of peptide supramolecular aggregation and the seeded supramolecular polymerization(SSP).In chapter 4,N-amidothioureas tailored with-SH group were allowed to react with Ag+ to form supramolecular coordination polymers.Supramolecular chirality is induced by the chirality transfer from phenylalanine residue to the thiourea moiety via the ?-turn structure.The ?-turn structure remains in the TFTU-Ag+ supramolecular polymers,and the supramolecular chirality is further transferred to the polymer leading to expression of the chirality at multi-levels.When breaking the ?-turn structure in TFTU,multi-level chirality disappears.The extent of the multi-level chirality expression is higher in the polymers with racemate enantiomers of TFTU and chiral TFTU tends to align in a quasi-racemate way,which is the major reason for the observed anti-"Z" shaped CD-e.e.curve.As a promising analytical tool to determine e.e.of value close to±100%,this kind of cleft supramolecular chirality could be a platform for the determination of both low e.e.and high e.e.values simultaneously.The research here manifests the role of ?-turn in guiding the design of cleft supramolecular chiral systems.