Role of the backbone conformation at position 7 in the structure and activity of marinostatin, an ester-linked serine protease inhibitor.

Rational design of inhibitors: The cis-amide backbone at position 7 in the serine protease inhibitor marinostatin was replaced with an E or Z olefin. The E olefin analogue was not active, but the Z analogue was. The cis conformation might play a critical role in organizing a canonical structure for binding to proteases.