Sortase A Inhibitors: Recent Advances and Future Perspectives

被引:114
作者
Cascioferro, Stella [1 ,2 ]
Raffa, Demetrio [1 ]
Maggio, Benedetta [1 ]
Raimondi, Maria Valeria [1 ]
Schillaci, Domenico [1 ]
Daidone, Giuseppe [1 ]
机构
[1] Univ Palermo, Dipartimento Sci & Tecnol Biol Chim & Farmaceut, Sez Chim & Tecnol Farmaceut, I-90123 Palermo, Italy
[2] Ist Euromediterraneo Sci & Tecnol, IEMEST, I-90139 Palermo, Italy
关键词
STAPHYLOCOCCUS-AUREUS SORTASE; PROTEIN ANCHORING TRANSPEPTIDASE; IMIDAZOLIUM ION-PAIR; SURFACE-PROTEINS; CELL-WALL; SRTA GENE; STREPTOCOCCUS-PNEUMONIAE; LISTERIA-MONOCYTOGENES; SORTING SIGNAL; A INHIBITORS;
D O I
10.1021/acs.jmedchem.5b00779
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Here, we describe the most promising small synthetic organic compounds that act as potent Sortase A inhibitors and cater the potential to be developed as antivirulence drugs. Sortase A is a polypeptide of 206 amino acids, which catalyzes two sequential reactions: (i) thioesterification and (ii) transpeptidation. Sortase A is involved in the process of bacterial adhesion by anchoring LPXTG-containing proteins to lipid II. Sortase A inhibitors do not affect bacterial growth, but they restrain the virulence of pathogenic bacterial strains, thereby preventing infections caused by Staphylococcus aureus or other Gram-positive bacteria. The efficacy of the most promising inhibitors needs to be comprehensively evaluated in in vivo models of infection, in order to select compounds eligible for the treatment of bacterial infections in humans.
引用
收藏
页码:9108 / 9123
页数:16
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