Peptide drug leads with increased inhibitory properties synthesized using a divergent strategy

Feb 6, 2018 2:01:22 PM

Protein-protein interactions (PPI) play a major role in regulating many cellular processes, which makes them attractive druggable targets. The large surface area involved in PPIs, however, demands high selectivity of large drug leads such as proteins that can be difficult to modify and fine-tune. To demonstrate a solution to this problem, Christian Tornøe and his colleagues at Novo Nordisk in Denmark have synthesized analogues of Bowman-Birk protease inhibitor (BBI) by using native chemical ligation of peptide hydrazides to link together peptide building blocks to generate several analogues of BBI. This approach required fewer reaction steps than a linear synthesis strategy, and could be used to graft a specific region of a potent trypsin inhibitor onto the α- chymotrypsin-binding loop of BBI that boosted its inhibitory effect four-fold. 


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Topics: Peptide synthesis, Protein-Protein Interactions (PPIs), Prelude peptide synthesizer