MENU ▼
Read by QxMD icon Read
search
OPEN IN READ APP
JOURNAL ARTICLE

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

Inmaculada Rentero Rebollo, Shawna McCallin, Davide Bertoldo, José Manuel Entenza, Philippe Moreillon, Christian Heinis
ACS Medicinal Chemistry Letters 2016 June 9, 7 (6): 606-11
27326335
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), suggesting that the macrocycles bind to the enzyme's active site and that they form similar molecular contacts as natural substrates. The evolved peptide macrocycles may be used as lead structures for the development of potent peptidomimetic SrtA inhibitors.

Comments

You need to log in or sign up for an account to be able to comment.

No comments yet, be the first to post one!

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
27326335
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"