Discovery of novel RIP derivatives by alanine scanning for the treatment of S. aureus infections

Alanine scanning has been used to define the key residues for the activity of RNA III inhibiting peptide (RIP) against S. aureus. We have found that the threonine residue at position 5 is detrimental to the RIP activity, while the removal of serine (P2) and phenylalanine (P7) afforded the most active RIP derivatives (2 and 7). Moreover, we have identified the small RIP derivative (9), corresponding to the sequence H-Ser-Pro-Trp-Thr-NH2, which displayed the best antistaphylococcal activity.