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Sökning: onr:"swepub:oai:lup.lub.lu.se:d01a4baf-8e48-4873-902f-e0d5bd657761" > Structure-Guided De...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005664naa a2200529 4500
001oai:lup.lub.lu.se:d01a4baf-8e48-4873-902f-e0d5bd657761
003SwePub
008211203s2021 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/d01a4baf-8e48-4873-902f-e0d5bd6577612 URI
0247 a https://doi.org/10.1021/acsmedchemlett.1c003712 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 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
2451 0a 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 1b 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 7a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe
650 7a 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
7001 a Baussière, Florianeu Lund University4 aut
7001 a Guzelj, Samou University of Ljubljana4 aut
7001 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
7001 a Håkansson, Mariau SARomics Biostructures AB4 aut
7001 a Kovačič, Rebekau SARomics Biostructures AB4 aut
7001 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
7001 a Tomašič, Tihomiru University of Ljubljana4 aut
7001 a Anderluh, Markou University of Ljubljana4 aut0 (Swepub:lu)ma3256an
7001 a Jakopin, Žigau University of Ljubljana4 aut
7001 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
7102 a Centrum för analys och syntesb Kemiska institutionen4 org
7730 t ACS Medicinal Chemistry Lettersd : American Chemical Society (ACS)g 12:11, s. 1745-1752q 12:11<1745-1752x 1948-5875
8564 u http://dx.doi.org/10.1021/acsmedchemlett.1c00371x freey FULLTEXT
8564 u https://pubs.acs.org/doi/pdf/10.1021/acsmedchemlett.1c00371
8564 8u https://lup.lub.lu.se/record/d01a4baf-8e48-4873-902f-e0d5bd657761
8564 8u https://doi.org/10.1021/acsmedchemlett.1c00371

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