Molecular Recognition And Spontaneous Resolution Of Folded Short Peptides

Proteins,having abundant secondary structures such as α-helix,β-sheet and β-turn that provide sufficient guarantee for the implementation of various functions in organisms,play a significant role in life activities.In recent years,α-helix and β-sheet,which are called "ridgepole" and "beam",have drawn extensive research attention.While β-turn,widely known as the most common turn structure,is also preferred as there are a rich number of binding sites in such structures of proteins.In this dissertation,peptide-based N-amidothiourea bearing β-turn is used as the structural motif while pyrene fluorophores are introduced to the termini of Namidothioureas,leading to peptide beacons for anion recognition based on bilateral βturns folded conformation.In addition,the folded short peptides substituted by halogen atom are designed and synthesized,and a single-stranded helix driven by C-I…O halogen bonding is constructed in the solid phase.With the help of the synergistic interaction of the halogen bonding and hydrogen bonding,homochiral assembly behavior is realized as well during the crystallization process,which results in a 2D chiral spontaneous resolution.The dissertation contains three chapters.Chapter 1 is the preface.β-Turn structure and azapeptides are described briefly at first,followed by the research progress of peptide beacon,supramolecular selfassembly and chiral spontaneous resolution by crystallization.Next,examples of peptide beacons based on double pyrene fluorophores and supramolecular helices constructed by helical fragments are discussed especially.Lastly,the research objectives and design schemes of this thesis are presented on the basis of the research background of our research group.In Chapter 2,a series of bilateral peptide-based N-amidothioureas la,1b and 1c are designed and synthesized to build folded peptide beacons.The folded conformation brings the two pyrene fluorophores into close proximity,triggering the formation and fluorescence of excimer.The thiourea group,anion receptor,transforms the beacon conformational changes into a fluorescent response signal.Among these beacons,the intensity ratio of excimer to monomer is in consistent with the strength of the β-turn,that 1b,containing medium strength of β-turns,exhibits the most sensitive response.The control compound 2 could not form β-turn structure due to the absence of amino acid residues.The control compound 3 is a single β-turn N-amidothiourea derivative containing one pyrene motif.Neither of control compounds can operate beacon-like sensing to show dramatic ratiometric fluorescence response,which reveals that the bilateral β-turns folded conformation plays a critical role in the working mechanism of these molecular beacons.This work affords a feasible structural scaffold,bilateral folded azapeptides,to perform beacon-like sensing,and also a regulation scheme to enhance the performance of peptide-based beacons by adjusting the stability of the folded conformation.On this basis,it is expected that peptide beacons with better sensor performance can be constructed.In chapter 3,folded short peptide mIA containing a m-iodobenzoyl is designed and synthesized.NMR,crystal structures and CD spectra confirm the existence of β-turn structure in mIA.The crystal structure shows that the supramolecular helix in the solid phase of mIA is driven by the intermolecular C-I…O halogen bond and 2D spontaneous resolution is realized in the crystallization of rac-mIA.It is found from the crystal data that the addition of heterochiral components will not destroy the supramolecular 2D helical plane structure of homochiral components,which is stabilized by intra-helix halogen bonds and inter-helix hydrogen bonds,and enhances with the help of strongly directional C-I…O halogen bond the propagation of β-turn helicity and the stability of homochiral helices.At the same time,the hydrogen bonding network connects the homochiral helices,leading to the formation of supramolecular homochiral helical plane.This may help to establish some new strategy for the rational design of chiral spontaneous resolution systems.