J 2018

Synthesis of a-L-fucopyranoside-presenting glycoclusters and investigation of their interaction with recombinant Photorhabdus asymbiotica lectin (PHL)

JANČAŘÍKOVÁ, Gita, Mihály HERCZEG, Eva FUJDIAROVÁ, Josef HOUSER, Katalin E. KÖVÉR et. al.

Basic information

Original name

Synthesis of a-L-fucopyranoside-presenting glycoclusters and investigation of their interaction with recombinant Photorhabdus asymbiotica lectin (PHL)

Authors

JANČAŘÍKOVÁ, Gita (203 Czech Republic, belonging to the institution), Mihály HERCZEG (348 Hungary), Eva FUJDIAROVÁ (203 Czech Republic, belonging to the institution), Josef HOUSER (203 Czech Republic, belonging to the institution), Katalin E. KÖVÉR (348 Hungary), Anikó BORBÁS (348 Hungary), Michaela WIMMEROVÁ (203 Czech Republic, guarantor, belonging to the institution) and Magdolna CSÁVÁS (348 Hungary)

Edition

Chemistry - A European Journal, VCH, 2018, 0947-6539

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 5.160

RIV identification code

RIV/00216224:14740/18:00102210

Organization unit

Central European Institute of Technology

DOI

UT WoS

000427563000023

Keywords in English

fucoclusters; lectin; multivalency; Photorhabdus asymbiotica; agglutination

Tags

Tags

International impact, Reviewed
Změněno: 28/3/2019 14:16, prof. RNDr. Michaela Wimmerová, Ph.D.

Abstract

V originále

Photorhabdus asymbiotica is a gram-negative bacterium that is not only as effective an insect pathogen as other members of the genus, but it also causes serious diseases in humans. The recently identified lectin PHL from P. asymbiotica verifiably modulates an immune response of humans and insects, which supports the idea that the lectin might play an important role in the host-pathogen interaction. Dimeric PHL contains up to seven L- fucose specific binding sites per monomer, and in order to target multiple binding sites of PHL, a-L-fucoside-containing di-, tri- and tetravalent glycoclusters were synthesized. Methyl gallate and pentaerythritol were chosen as multivalent scaffolds, and the fucoclusters were built from the above-mentioned cores by coupling with different oligoethylene bridges and propargyl a-L-fucosides using 1,3-dipolar azide-alkyne cycloaddition. The interaction between fucoside derivates and PHL was investigated by several biophysical and biological methods, ITC and SPR measurements, hemagglutination inhibition assay and an investigation of bacterial aggregation properties were carried out. Moreover, details of the interaction between PHL and propargyl a-L-fucoside as a monomer unit were revealed using X-ray crystallography. Besides this, the interaction with multivalent compounds was studied by NMR techniques. The newly synthesized multivalent fucoclusters proved to be up to several orders of magnitude better ligands than the natural ligand, L-fucose.

Links

CZ.02.1.01/0.0/0.0/16_013/0001776, interní kód MU
(CEP code: EF16_013/0001776)
Name: CIISB - Česká infrastruktura pro integrativní strukturní biologii pro lidské zdraví (Acronym: CIISB4HEALTH)
Investor: Ministry of Education, Youth and Sports of the CR, Czech Infrastructure for Integrative Structural Biology for Human Health, Priority axis 1: Strengthening capacities for high-quality research
LM2015043, research and development project
Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
LTC17076, research and development project
Name: Interdisciplinární přístup ke studiu biologických systémů na molekulární úrovni
Investor: Ministry of Education, Youth and Sports of the CR, Interdisciplinary approach to study biological systems at the molecular level, INTER-COST