“…Optimization steps include the insertion of unnatural amino acids, side-chain or backbone modifications, terminus protection via amidation or acetylation and cyclization reactions including novel cyclization techniques such as peptide stapling and head to tail closing. 6,20–28 The advantages of these optimized peptidomimetics include higher stability towards proteolysis, higher conformational stability, better transport properties across membranes and a higher target affinity depending on the chosen modification. 15,26,27,29,30 This was observed in the optimization process of dengue and West Nile virus protease inhibitor of 763 Da with membrane permeability and metabolic stability containing 4-benzyloxyphenylglycine derivative and a bithiophene N-cap.…”