Biomedical polyurethane (BPU) and silk fibroin have similarly molecular architecture in their primary and aggregate structure, both of which have amide bonds and microphase separation, and they have been employed as scaffold materials for biomedical applications. Based on this, as the featured peptide sequence of silkworm silk fibroin, GlycineAlanineGlycineAlanine (GlyAlaGlyAla) tetrapeptide was synthesized by using traditional liquid-phase peptide synthesis method with Boc-protected glycine and alanine as starting materials, and was transformed to its derivative with two amine-terminated functional groups. The derivative was introduced as a chain extender into the backbone to form the hard segment of a silk-inspired PU with urea-linkage. Related measurements show that molecular weight of the synthesized silk-inspired PU ranged from 13,000 to 15,000. Fourier transform infrared (FTIR) absorption bands of Amides I and II are at 1651 cm(-1) and 1534 cm(-1), and Raman absorption band of Amide III is at 1302 cm(-1). UV-Vis absorption peak of the silk-inspired PU is at 266 nm. This new concept and strategy may allow the fabrication of a new class of thermoplastic polyurethane elastomers to mimic the structure and properties of silk fibroin of silkworms and spiders. Information provided by this study may be used to better understand the correlation between the natural and man-made materials. (c) 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013