Sequential addition of benzyl-L-glutamate and tert-butyl-L-glutamate N-carboxyanhydrides (NCAs) under optimized reaction conditions was used to synthesize block-sequence-defined polypeptides. Alternating octablock, tetrablock, and diblock as well as statistical polypeptides were obtained with comparable total compositions and total number of units. All of them were able to adopt helical secondary structures. Selective deprotection of the tert-butyl side chain yielded polypeptides with alternating benzyl-L-glutamate and L-glutamic acid block sequences available for further selective modification of individual block sequences. This was exploited for the conjugation with PEG side chains selectively on the glutamic acid block sequences. A detailed investigation revealed significant differences in properties as a function of the block-sequenced composition. Polypeptides with shorter alternating block sequences showed better water solubility. Dynamic light scattering revealed the presence of individual polypeptide chains in water in the case of the octablock polypeptide, while increasing aggregation was observed with increasing block length as well as for the statistical polypeptide. Moreover, the octablock polypeptide displayed a defined cloud point at 60 degrees C, while no defined transition could be observed with any of the other polypeptide block sequences. The results demonstrate the dependence of polypeptide properties on their block-sequenced composition and open opportunities for a polymerization approach complementary to the stepwise synthesis of peptidomimetics.