The Synthesis And Characterization Of Dendronized Polypeptides And Amphiphilic Dendritic Macromolecules

This dissertation includes two parts:(1) to investigate the secondary structures of peptidesunder constrained conditions is very important to help to understand the rules that proteins playin bioactivities. Dendronized polypeptides combine the structural characteristics and propertiesfrom both dendronized polymers and polypeptides, and are promising in biomedical applicationsand bio-related tissue engineering.(2) Amphiphilic dendritic molecules possess highly branchedand symmetric structures with excellent self-assembly behavior, and promising applications inbiomedical and nanomaterials. In this dissertation, the synthesis and characterization of thethermoresponsive dendronized polypeptides and polypeptides brushes with novel structures, aswell as the thermoresponsive properties of oligo(ethylene glycol) based amphiphilic dendriticmolecules are investigated. It is divided into four parts:1. Synthesis and characterization of dendronized polyprolinesThe oligo(ethylene glycol)(OEG) based dendronized polyprolines with sequential structuresare efficiently synthesized via both “Grafting to” route and “Macromonomer” route. Thethermoresponsive properties and secondary structure stability of these dendronized polyprolinesare investigated. The thermoresponsiveness of the polymers are dependent on the dendronstructures (the periphery groups and generation of the dendron), as well as the arrangement of thedendrons along the polyproline backbones. For the study of the conformational stability, thebackbone conformations are not only dependent on dendron generations (G1and G2), but alsoon configurations of the4th position of the pyrrolidine ring of the proline (4S or4R) in thebackbone. More interestingly, when the solution temperature is increased around their LCSTs,the dendronized polyprolines prefer to retain PPI conformation or undergo the conformationaltransion from PPII to PPI. This is the first example by changing the temperature to mediate thepolyproline conformational transition from PPI to PPII. These findings are important for theunderstanding of the conformation stability of the polypeptides or proteins in the constrainedconditions.In addition, Atomic Force Microseopy (AFM) techniques are utilized for the first time to “view” the conformation transformation of dendronized polyprolines from PPI to PPII.2. Poly-L-Tyrosines functionalized with Oligo(ethylene glycol)Poly-L-Tyrosines (PLTs) functionalized with oligo(ethylene glycol)s were prepared for thefirst time via one-step reaction based on the Williamson reaction between PLT and tri(ethyleneglycol)(TEG) as well as the corresponding Oligo(ethylene glycol)(OEG) dendron (EtG1)。Thethermoresponsiveness and secondary structures of PLT-TEG and PLT-G1are investigated.PLT-TEG can not be dissolved in H2O, but PLT-G1is soluble well in H2O and shows excellentthermoresponsive properties with a cloud point temperature (Tcp) around36oC. This syntheticefficient procedure provides a new insight for the synthesis of stimuli-responsive polypeptides.3. Peptidic molecular brushes based on prolinesA series of high molecular weight molecular brushes constructed with poly (methylmethacrylate) backbone and the rigid second-generation dendron based on(2S,4S)-4-aminoprolines are synthesized via macromonomer route. The spacers between thedendrons and the polymer backbones are designed to be flexible OEG chains with differentlengths and rigid oligoprolines (dipeptide, P2or octapeptide, P8). The backbone rigidities ofthese polymers are investigated with AFM. It is interesting to find that the polymer chains withOEG as spacers show very flexible morphologies on mica surface. With P2as spacer, thepolymer chains still exhibits flexible conformation. A significant rigidity enhancement ofpolymer chains was observed when the spacer is replaced with P8spacer.Considering the very stable PPII conformations adopted by P8spacer, the significantrigidity enhancement of the polymer backbone mostly comes from the high steric hindranceinduced by P8spacer in PPII helix. This is the first example to mediate the rigidity of polymerbackbone by changing the side chain oligopeptide conformations.4. Synthesis and characterization of oligo(ethylene glycol) based amphiphilic dendriticmacromoleculesA series of OEG-based amphiphilic dendritic macromolecules are designed and efficientlysynthesized. These amphiphilic molecules are constructed with OEG dendron (EtG1and MtG1)and dendritic aliphatic chains with different length. The thermoresponsiveness of these dendriticmacromolecules are investigated. It was found that all the molecules show characteristic thermoresponsive properties with different phase transition temperatures. Notably, the structuresof the dendritic molecules with appropriate hydrophilic and hydrophobic balance exhibitmulti-temperature responsive properties. As the temperature increases slowly, their aqueoussolution changes in the following sequence: transparent--opaque--less transparent--opaque, andthis process is reversible as decreasing temperature. The phase transition temperatures of everystage were shifted with the change of the dendron or length of the aliphatic chain. These findingsenrich the understanding of structure effects on their thermoresponsiveness.