Metallo-β-Lactamase Inhibitor Phosphonamidate Monoesters

Palica, Katarzyna,1992-Uppsala University,Uppsala universitet,Organisk kemi (author)

Being the second leading cause of death and the leading cause of disability-adjusted life years worldwide, infectious diseases remain─contrary to earlier predictions─a major consideration for the public health of the 21st century. Resistance development of microbes to antimicrobial drugs constitutes a large part of this devastating problem. The most widely spread mechanism of bacterial resistance operates through the degradation of existing β-lactam antibiotics. Inhibition of metallo-β-lactamases is expected to allow the continued use of existing antibiotics, whose applicability is becoming ever more limited. Herein, we describe the synthesis, the metallo-β-lactamase inhibition activity, the cytotoxicity studies, and the NMR spectroscopic determination of the protein binding site of phosphonamidate monoesters. The expression of single- and double-labeled NDM-1 and its backbone NMR assignment are also disclosed, providing helpful information for future development of NDM-1 inhibitors. We show phosphonamidates to have the potential to become a new generation of antibiotic therapeutics to combat metallo-β-lactamase-resistant bacteria.

Vorácová, ManuelaUppsala University,Uppsala universitet,Institutionen för kemi - BMC (author)
Skagseth, SusannThe Norwegian Structural Biology Centre (NorStruct), Department of Chemistry, Faculty of Science and Technology, UiT The Arctic University of Norway, N-9037 Tromsø, Norway (author)
Andersson Rasmussen, AnnaUppsala University,Lund University,Lunds universitet,Uppsala universitet,Institutionen för kemi - BMC,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Molecular Cell Biology,Department of Biology,Faculty of Science(Swepub:lu)cob-ars (author)
Allander, LisaUppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)lisal119 (author)
Hubert, MadlenUppsala University,Uppsala universitet,Institutionen för farmaci(Swepub:uu)madhu517 (author)
Sandegren, LinusUppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi(Swepub:uu)lisan839 (author)
Schrøder Leiros, Hanna-KirstirepThe Norwegian Structural Biology Centre (NorStruct), Department of Chemistry, Faculty of Science and Technology, UiT The Arctic University of Norway, N-9037 Tromsø, Norway (author)
Andersson, Hanna,Dr.1979-Uppsala universitet,Organisk kemi(Swepub:uu)haand498 (author)
Erdélyi, Máté,1975-Uppsala University,Uppsala universitet,Organisk kemi(Swepub:uu)mateerde (author)
Leiros, Hanna-KirstUiT The Arctic University of Norway, Tromsø (author)
Uppsala universitetOrganisk kemi (creator_code:org_t)

By the author/editor: Palica, Katarzyn ...; Vorácová, Manuel ...; Skagseth, Susann; Andersson Rasmus ...; Allander, Lisa; Hubert, Madlen; show more...; Sandegren, Linus; Schrøder Leiros, ...; Andersson, Hanna ...; Erdélyi, Máté, 1 ...; Leiros, Hanna-Ki ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

NATURAL SCIENCES: NATURAL SCIENCES; and Chemical Science ...; and Organic Chemistr ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.