Chemo-enzymatic synthesis of LacdiNAc dimers of varying length as novel galectin ligands

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F14%3A10400183" target="_blank" >RIV/00216208:11320/14:10400183 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/14:00428358

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3f.6Zx2rkq" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=3f.6Zx2rkq</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molcatb.2013.12.018" target="_blank" >10.1016/j.molcatb.2013.12.018</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Chemo-enzymatic synthesis of LacdiNAc dimers of varying length as novel galectin ligands

Popis výsledku v původním jazyce

A set of sixteen bivalent symmetrical and asymmetrical LacdiNAc dimers containing flexible alkyl linkers were efficiently synthesized by means of chemo-enzymatic synthesis, using the versatile potential of the Y284L mutant of human placental beta 1,4-galactosyltransferase-1. LacdiNAc was confirmed to be a specific ligand for human galectin-3 contrary to human galectin-1. The compounds were tested as ligands for human galectin-3 in competitive binding assays and compared to a monovalent LacdiNAc standard. Molecular modeling was performed to calculate approximate length of respective ligands and its relation to their inhibitory capacity. The best performance was observed in symmetrical compounds carrying two LacdiNAc units connected with a hydrophobic linker of sufficient length (alkyl chain n &gt;= 6). Here, the IC50 value was about three times lower than that of the monovalent standard. Our results propose that hydrophobicity directed by the alkyl chain length as well as the specificity and bivalency of the LacdiNAc contribute to the inhibition potential of these ligands. Though only slightly pronounced in this case, higher multivalency is a promising feature in the design of optimized ligands for galectin-3. (C) 2014 Elsevier B.V. All rights reserved.

Název v anglickém jazyce

Chemo-enzymatic synthesis of LacdiNAc dimers of varying length as novel galectin ligands

Popis výsledku anglicky

A set of sixteen bivalent symmetrical and asymmetrical LacdiNAc dimers containing flexible alkyl linkers were efficiently synthesized by means of chemo-enzymatic synthesis, using the versatile potential of the Y284L mutant of human placental beta 1,4-galactosyltransferase-1. LacdiNAc was confirmed to be a specific ligand for human galectin-3 contrary to human galectin-1. The compounds were tested as ligands for human galectin-3 in competitive binding assays and compared to a monovalent LacdiNAc standard. Molecular modeling was performed to calculate approximate length of respective ligands and its relation to their inhibitory capacity. The best performance was observed in symmetrical compounds carrying two LacdiNAc units connected with a hydrophobic linker of sufficient length (alkyl chain n &gt;= 6). Here, the IC50 value was about three times lower than that of the monovalent standard. Our results propose that hydrophobicity directed by the alkyl chain length as well as the specificity and bivalency of the LacdiNAc contribute to the inhibition potential of these ligands. Though only slightly pronounced in this case, higher multivalency is a promising feature in the design of optimized ligands for galectin-3. (C) 2014 Elsevier B.V. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Molecular Catalysis B - Enzymatic

ISSN

1381-1177

e-ISSN

—

Svazek periodika

101

Číslo periodika v rámci svazku

101

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

9

Strana od-do

47-55

Kód UT WoS článku

000332142400008

EID výsledku v databázi Scopus

2-s2.0-84892919230