Design and development of 206 178 sheet polypeptides for biomedical applications

Abstract

Synthetic polypeptides are continued to be one of the most challenging area to mimic the properties of the natural biomolecules (i.e, proteins) in macromolecular systems for both fundamental understanding and new technology development. and#61538;-Sheet forming polypeptides are one of the least explored synthetic systems and this main restriction is associated with the uncontrollable-precipitation of the polymer chains during their synthesis. As a result, the and#61538;-sheet polymerization was found to be non-living with dead propagation chains and they were inefficient for the synthesis of block copolymer architectures. This important problem in polypeptide area is addressed in this thesis work by developing new steric-hindrance ring opening polymerization strategy by controlling the helicity of the propagating polymer chains. New bulky N-carboxyanhydride (NCA) monomers were designed having t-butylbenzene pendant by multi-step organic synthesis and N-heterocyclic carbene was explored as a catalyst to make high molecular weight and narrow polydisperse soluble polypeptides. This ROP process was successfully demonstrated for two and#61538;-sheet forming polypeptides such as poly(and#671;-serine) and poly(and#671;-cysteine). These new t-butylbenzene functionalized polypeptides were found to be readily soluble in tetrahydrofuran and chloroform, etc, and they were produced in high molecular weights having Mn = 32 kDa with dispersity and#272; and#61603; 1.3. ROP kinetics were studied by real-time FT-IR and 1H-NMR to determine the actual content of the secondary structures in the propagating chains. These studies established that and#61537;-helical conformational front in the propagation chain was speeding up the polymerization kinetics with good degree of control in the ROP process. Reversible-conformational transitions in the post polymerization deprotection was found to restore the and#61538;-sheet secondary structures in poly(and#671;-serine)s. Furthermore, the scope of this approach was expanded for the building inaccessible block copolymer macromolecular architectures. The serine-glutamate