title: The development of first Staphylococcus aureus SplB protease inhibitors: phosphonic analogues of glutamine.
abstract: Produced by Staphylococcus aureus, SplB belongs to the chymotrypsin-like serine protease family. Since the biological role of SplB protease is unknown, the design and application of its specific inhibitors may help to reveal the function of this enzyme. Until now no SplB inhibitors have been reported. Herein, we present the design and synthesis of novel α-aminophosphonic analogues of glutamine, as well as their peptidyl derivatives. The inhibitory effects of these compounds towards the newly discovered SplB serine protease from S. aureus are characterized. We have also investigated the influence of aromatic ester substituents on inhibitory potency towards SplB. One of the compounds-Cbz-Glu-Leu-Gln(P)(OC(6)H(4)-4-O-CH(3))(2)-displayed an apparent second-order inhibition rate value of 1400 M(-1)s(-1).
authors.affiliation: Division of Medicinal Chemistry and Microbiology, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Burchacka
authors.initials: B
authors.lastname: Ewa
authors.forename: Walczak
authors.initials: W
authors.lastname: Maciej
authors.forename: Sieńczyk
authors.initials: S
authors.lastname: Marcin
authors.forename: Dubin
authors.initials: D
authors.lastname: Grzegorz
authors.forename: Zdżalik
authors.initials: Z
authors.lastname: Michał
authors.forename: Potempa
authors.initials: P
authors.lastname: Jan
authors.forename: Oleksyszyn
authors.initials: O
authors.lastname: Józef
mesh_terms: D005973:Glutamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D057057:Serine Proteases / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology*
chemical_list: D015842:Serine Proteinase Inhibitors; D005973:Glutamine; D057057:Serine Proteases