Polypeptides from L-amino acid bioresources are remarkable macromolecular biomaterials for applications in tissue engineering, drug and gene delivery, etc. Synthetic methodologies are largely well-established for freely soluble α-helical polypeptides and they contribute to 99 % of the existing knowledge in the literature. On the contrary, b-sheet polypeptides are one of the least explored polymer systems due to their uncontrolled precipitation during synthesis and non-living characteristics of the propagating chain-ends. This challenging task was recently solved by us by introducing steric-controlled ring opening polymerization strategy in which the initial polypeptide chains were propagated in α-helical conformation and post-polymerization deprotection was employed to restore their original b-sheet conformation as and when required. t-Butylbenzene group was identified as structure directing-cum-solubilizing handle for this purpose, and the proof-of-concept was demonstrated successfully in b-sheet polypeptides based on poly(ʟ-serine), poly(ʟ-cysteine) and poly(ʟ-tyrosine), etc. Steric-handle facilitated the a-helical conformational front in the propagating chain to become soluble and high molecular weight living chains so that they could subsequently be employed as macro-initiators to build variety of unexplored β-sheet di-block and tri-block copolymers. These block copolymers open a new avenue for several amphiphilic polypeptides with well-defined architectures and are currently being investigated for biomedical applications in vitro and in vivo. The presentation will highlight the importance of b-sheet polypeptides and their future perspectives.