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Search: WFRF:(Schelin M) > (2020-2024) > Sialic Acid Derivat...

Sialic Acid Derivatives Inhibit SiaT Transporters and Delay Bacterial Growth

Bozzola, Tiago (author)
Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,University of Basel
Scalise, M. (author)
University of Calabria
Larsson, Christer U. (author)
Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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Newton-Vesty, M. C. (author)
Canterbury University
Rovegno, C. (author)
Lund University
Mitra, Ankita (author)
Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
Cramer, J. (author)
University of Basel,Heinrich Heine University Düsseldorf,Canterbury University
Wahlgren, Weixiao Yuan, 1970 (author)
University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
Santhakumari, P. R. (author)
Manipal Academy of Higher Education
Johnsson, R. E. (author)
Schwardt, O. (author)
University of Basel
Ernst, B. (author)
University of Basel
Friemann, Rosmarie, 1975 (author)
University of Gothenburg,Gothenburg University,Göteborgs universitet,CARe - Centrum för antibiotikaresistensforskning,Centre for antibiotic resistance research, CARe,Sahlgrenska University Hospital
Dobson, R. C. J. (author)
Indiveri, C. (author)
University of Calabria
Schelin, Jenny (author)
Lund University,Lunds universitet,Förpackningslogistik,Institutionen för designvetenskaper,Institutioner vid LTH,Lunds Tekniska Högskola,Teknisk mikrobiologi,Centrum för tillämpade biovetenskaper,Kemiska institutionen,Läkemedelsteknologi (master),Utbildningsprogram, LTH,Packaging Logistics,Department of Design Sciences,Departments at LTH,Faculty of Engineering, LTH,Applied Microbiology,Center for Applied Life Sciences,Department of Chemistry,Faculty of Engineering, LTH,Pharmaceutical Technology (master),Educational programmes, LTH,Faculty of Engineering, LTH
Nilsson, Ulf J. (author)
Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
Ellervik, Ulf (author)
Lund University,Lunds universitet,Lungbiologi,Forskargrupper vid Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Lung Biology,Lund University Research Groups,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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 (creator_code:org_t)
2022-06-08
2022
English.
In: Acs Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 17:7, s. 1890-1900
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Antibiotic resistance is a major worldwide concern, and new drugs with mechanistically novel modes of action are urgently needed. Here, we report the structure-based drug design, synthesis, and evaluation in vitro and in cellular systems of sialic acid derivatives able to inhibit the bacterial sialic acid symporter SiaT. We designed and synthesized 21 sialic acid derivatives and screened their affinity for SiaT by a thermal shift assay and elucidated the inhibitory mechanism through binding thermodynamics, computational methods, and inhibitory kinetic studies. The most potent compounds, which have a 180-fold higher affinity compared to the natural substrate, were tested in bacterial growth assays and indicate bacterial growth delay in methicillin-resistant Staphylococcus aureus. This study represents the first example and a promising lead in developing sialic acid uptake inhibitors as novel antibacterial agents.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

Keyword

resistance
glycosylation
Biochemistry & Molecular Biology

Publication and Content Type

ref (subject category)
art (subject category)

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