Search: onr:"swepub:oai:lup.lub.lu.se:d01a4baf-8e48-4873-902f-e0d5bd657761" > Structure-Guided De...
Fältnamn | Indikatorer | Metadata |
---|---|---|
000 | 05664naa a2200529 4500 | |
001 | oai:lup.lub.lu.se:d01a4baf-8e48-4873-902f-e0d5bd657761 | |
003 | SwePub | |
008 | 211203s2021 | |||||||||||000 ||eng| | |
024 | 7 | a https://lup.lub.lu.se/record/d01a4baf-8e48-4873-902f-e0d5bd6577612 URI |
024 | 7 | a https://doi.org/10.1021/acsmedchemlett.1c003712 DOI |
040 | a (SwePub)lu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a art2 swepub-publicationtype |
072 | 7 | a ref2 swepub-contenttype |
100 | 1 | a Hassan, Mujtabau 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 Ljubljana4 aut0 (Swepub:lu)mu2462ha |
245 | 1 0 | a Structure-Guided Design of d -Galactal Derivatives with High Affinity and Selectivity for the Galectin-8 N-Terminal Domain |
264 | c 2021-11-02 | |
264 | 1 | b American Chemical Society (ACS),c 2021 |
300 | a 8 s. | |
520 | a Galectin-8 is a carbohydrate-binding protein that plays a crucial role in tumor progression and metastasis, antibacterial autophagy, modulation of the immune system, and bone remodeling. The design, synthesis, and protein affinity evaluation of a set of C-3 substituted benzimidazole and quinoline d-galactal derivatives identified a d-galactal-benzimidazole hybrid as a selective ligand for the galectin-8 N-terminal domain (galectin-8N), with a Kd of 48 μM and 15-fold selectivity over galectin-3 and even better selectivity over the other mammalian galectins. X-ray structural analysis of galectin-8N in complex with one benzimidazole- and one quinoline-galactal derivative at 1.52 and 2.1 Å together with molecular dynamics simulations and quantum mechanical calculations of galectin-8N in complex with the benzimidazole derivative revealed orbital overlap between a NH LUMO of Arg45 with electron rich HOMOs of the olefin and O4 of the d-galactal. Such overlap is hypothesized to contribute to the high affinity of the d-galactal-derived ligands for galectin-8N. A (3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay evaluation of the d-galactal-benzimidazole hybrid and an analogous galactoside derivative on a panel of cell lines with MTS assay showed no effect on cell viability up to 100 μM concentration. A subsequent functional assay using the MDA-MB-231 cell line demonstrated that the d-galactal-benzimidazole hybrid and the analogous galactoside derivative reduced the secretion of the proinflammatory cytokines interleukin-6 (IL-6) and IL-8 in a dose-dependent manner. Therefore, these compounds represent potential probes for galectin-8N pharmacology investigations and possibly promising leads for the design and synthesis of potent and selective galectin-8 inhibitors as potential antitumor and anti-inflammatory agents. | |
650 | 7 | a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the medical area0 (SwePub)301102 hsv//eng |
653 | a benzimidazole | |
653 | a cytokine secretion | |
653 | a d -galactal | |
653 | a Galectin-8N | |
653 | a selectivity | |
653 | a X-ray crystallography | |
700 | 1 | a Baussière, Florianeu Lund University4 aut |
700 | 1 | a Guzelj, Samou University of Ljubljana4 aut |
700 | 1 | a Sundin, Anders P.u 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, LTH4 aut0 (Swepub:lu)ok2-aps |
700 | 1 | a Håkansson, Mariau SARomics Biostructures AB4 aut |
700 | 1 | a Kovačič, Rebekau SARomics Biostructures AB4 aut |
700 | 1 | a Leffler, Hakonu Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments4 aut0 (Swepub:lu)mmb-hle |
700 | 1 | a Tomašič, Tihomiru University of Ljubljana4 aut |
700 | 1 | a Anderluh, Markou University of Ljubljana4 aut0 (Swepub:lu)ma3256an |
700 | 1 | a Jakopin, Žigau University of Ljubljana4 aut |
700 | 1 | a Nilsson, Ulf J.u 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, LTH4 aut0 (Swepub:lu)ok2-uni |
710 | 2 | a Centrum för analys och syntesb Kemiska institutionen4 org |
773 | 0 | t ACS Medicinal Chemistry Lettersd : American Chemical Society (ACS)g 12:11, s. 1745-1752q 12:11<1745-1752x 1948-5875 |
856 | 4 | u http://dx.doi.org/10.1021/acsmedchemlett.1c00371x freey FULLTEXT |
856 | 4 | u https://pubs.acs.org/doi/pdf/10.1021/acsmedchemlett.1c00371 |
856 | 4 8 | u https://lup.lub.lu.se/record/d01a4baf-8e48-4873-902f-e0d5bd657761 |
856 | 4 8 | u https://doi.org/10.1021/acsmedchemlett.1c00371 |
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.
Copy and save the link in order to return to this view