Creation of novel signalling modulators from existing cytokine using scanning motif-programming f

摘要

We created two artificial modulating proteins for bone morpho-genetic protein (BMP)-signalling, tmw57 and tmw61, starting from partial sequences of human BMP-2 (hBMP-2). The proteins were able to boost the hBMP-4 activities, BMP responsive element-driven transcription and an osteoblastic differentiation marker induction. Convoluted signal transduction networks can be interpreted as accumulations of subtle but specific relationships among proteins. These relationships can often be reduced to interactions among short peptides (motifs) residing within the larger proteins. This provides us with the opportunity to develop novel biologics that modulate existing signal networks through motif programming. hBMP-2 is a disulfide-bonded homodimeric cytokine that induces bone formation and affects tumorigenesis.5 Here we show that novel modulators of BMP signalling can be created by reiterating parts of sequences from BMP-2.