Development of Potent and Selective S. aureus Sortase A Inhibitors Based on Peptide Macrocycles.

ABSTRACT: Sortases are transpeptidase enzymes that anchor surface proteins, including virulence factors, to the cell wall of Gram-positive bacteria, and they are potential targets for the development of anti-infective agents. While several large compound libraries were searched by high-throughput screening, no high-affinity inhibitors of sortases could be developed to date. Here, we applied phage display to screen billions of peptide macrocycles against sortase A (SrtA) of Staphylococcus aureus (S. aureus). We were able to identify potent and selective inhibitors of SrtA that blocked SrtA-mediated anchoring of synthetic substrates to the surface of live S. aureus cells. A region present in all inhibitory peptides (Leu-Pro-Pro) resembled the natural substrates of SrtA (Leu-Pro-Xaa-Thr-Gly), suggestin

SUBMITTER: Rentero Rebollo I 

PROVIDER: S-EPMC4904248 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature