Antimicrobial peptidomimetics against methycillin-resistant Staphylococcus aureus (MRSA)

Staphylococcus aureus is considered the leading cause of human diseases not only hospitalized individuals, but also in individuals living in the community.Staphylococcus aureus mainly causes skin infections, such as purulent wounds, soft tissue inflammation, impetigo, and may also cause inflammation of the endocardium, lungs, and bone marrow.The number of infections caused by MRSA strains is increasing around the world.WHO predicts that by 2050, mortality caused by AMR (antimicrobial resistance) will be one of the main causes of death.[1] In this work, we report the development of novel peptidyl derivatives based upon the structure of the N-terminal fragment (R 8 L 9 V 10 G 11 ) of the human cystatin C protein.A derivative called Cystapep 1 (A-20) has a strong activity against Gram-positive bacteria, including MRSA strains.[2] We synthesized analogues of Cystapep 1 with modifications at the highlighted site on Scheme 1.