Selectins-The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion
Molecules-A Review

J 2020

Selectins-The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules-A Review

TVAROŠKA, Igor; Selvaraj CHANDRABOSE a Jaroslav KOČA

Základní údaje

Originální název

Selectins-The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules-A Review

Autoři

TVAROŠKA, Igor (703 Slovensko, domácí); Selvaraj CHANDRABOSE (356 Indie, domácí) a Jaroslav KOČA (203 Česká republika, garant, domácí)

Vydání

Molecules, Basel, Academic Press, 2020, 1420-3049

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.412

Kód RIV

RIV/00216224:14740/20:00117929

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.3390/molecules25122835

UT WoS

000553873800001

EID Scopus

2-s2.0-85087011238

Klíčová slova anglicky

selectins; selectin ligands; carbohydrate determinants; sialyl Lewis x; glycosyltransferases; inflammation; cancer; selectin-ligand interactions; inhibitors; transition state analog inhibitors

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 14. 4. 2021 16:28, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Selectins belong to a group of adhesion molecules that fulfill an essential role in immune and inflammatory responses and tissue healing. Selectins are glycoproteins that decode the information carried by glycan structures, and non-covalent interactions of selectins with these glycan structures mediate biological processes. The sialylated and fucosylated tetrasaccharide sLe(x)is an essential glycan recognized by selectins. Several glycosyltransferases are responsible for the biosynthesis of the sLe(x)tetrasaccharide. Selectins are involved in a sequence of interactions of circulated leukocytes with endothelial cells in the blood called the adhesion cascade. Recently, it has become evident that cancer cells utilize a similar adhesion cascade to promote metastases. However, like Dr. Jekyll and Mr. Hyde's two faces, selectins also contribute to tissue destruction during some infections and inflammatory diseases. The most prominent function of selectins is associated with the initial stage of the leukocyte adhesion cascade, in which selectin binding enables tethering and rolling. The first adhesive event occurs through specific non-covalent interactions between selectins and their ligands, with glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains a principal strategy aimed at developing new therapies for the treatment of immune and inflammatory disorders and cancer. In this review, we will survey the significant contributions to and the current status of the understanding of the structure of selectins and the role of selectins in various biological processes. The potential of selectins and their ligands as therapeutic targets in chronic and acute inflammatory diseases and cancer will also be discussed. We will emphasize the structural characteristic of selectins and the catalytic mechanisms of glycosyltransferases involved in the biosynthesis of glycan recognition determinants. Furthermore, recent achievements in the synthesis of selectin inhibitors will be reviewed with a focus on the various strategies used for the development of glycosyltransferase inhibitors, including substrate analog inhibitors and transition state analog inhibitors, which are based on knowledge of the catalytic mechanism.

Návaznosti

EF17_050/0008496, projekt VaV

Název: MSCAfellow@MUNI

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

90070, velká výzkumná infrastruktura

Název: IT4Innovations

Citovat

TVAROŠKA, Igor; Selvaraj CHANDRABOSE a Jaroslav KOČA. Selectins-The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules-A Review. Molecules. Basel: Academic Press, 2020, roč. 25, č. 12, s. 1-61. ISSN 1420-3049. Dostupné z: https://dx.doi.org/10.3390/molecules25122835.

@article{1731236,
   author = {Tvaroška, Igor and Chandrabose, Selvaraj and Koča, Jaroslav},
   article_location = {Basel},
   article_number = {12},
   doi = {http://dx.doi.org/10.3390/molecules25122835},
   keywords = {selectins; selectin ligands; carbohydrate determinants; sialyl Lewis x; glycosyltransferases; inflammation; cancer; selectin-ligand interactions; inhibitors; transition state analog inhibitors},
   language = {eng},
   issn = {1420-3049},
   journal = {Molecules},
   title = {Selectins-The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules-A Review},
   url = {https://doi.org/10.3390/molecules25122835},
   volume = {25},
   year = {2020}
}

TY  - JOUR
ID  - 1731236
AU  - Tvaroška, Igor - Chandrabose, Selvaraj - Koča, Jaroslav
PY  - 2020
TI  - Selectins-The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules-A Review
JF  - Molecules
VL  - 25
IS  - 12
SP  - 1-61
EP  - 1-61
PB  - Academic Press
SN  - 14203049
KW  - selectins
KW  - selectin ligands
KW  - carbohydrate determinants
KW  - sialyl Lewis x
KW  - glycosyltransferases
KW  - inflammation
KW  - cancer
KW  - selectin-ligand interactions
KW  - inhibitors
KW  - transition state analog inhibitors
UR  - https://doi.org/10.3390/molecules25122835
L2  - https://doi.org/10.3390/molecules25122835
N2  - Selectins belong to a group of adhesion molecules that fulfill an essential role in immune and inflammatory responses and tissue healing. Selectins are glycoproteins that decode the information carried by glycan structures, and non-covalent interactions of selectins with these glycan structures mediate biological processes. The sialylated and fucosylated tetrasaccharide sLe(x)is an essential glycan recognized by selectins. Several glycosyltransferases are responsible for the biosynthesis of the sLe(x)tetrasaccharide. Selectins are involved in a sequence of interactions of circulated leukocytes with endothelial cells in the blood called the adhesion cascade. Recently, it has become evident that cancer cells utilize a similar adhesion cascade to promote metastases. However, like Dr. Jekyll and Mr. Hyde's two faces, selectins also contribute to tissue destruction during some infections and inflammatory diseases. The most prominent function of selectins is associated with the initial stage of the leukocyte adhesion cascade, in which selectin binding enables tethering and rolling. The first adhesive event occurs through specific non-covalent interactions between selectins and their ligands, with glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains a principal strategy aimed at developing new therapies for the treatment of immune and inflammatory disorders and cancer. In this review, we will survey the significant contributions to and the current status of the understanding of the structure of selectins and the role of selectins in various biological processes. The potential of selectins and their ligands as therapeutic targets in chronic and acute inflammatory diseases and cancer will also be discussed. We will emphasize the structural characteristic of selectins and the catalytic mechanisms of glycosyltransferases involved in the biosynthesis of glycan recognition determinants. Furthermore, recent achievements in the synthesis of selectin inhibitors will be reviewed with a focus on the various strategies used for the development of glycosyltransferase inhibitors, including substrate analog inhibitors and transition state analog inhibitors, which are based on knowledge of the catalytic mechanism.
ER  -

TVAROŠKA, Igor; Selvaraj CHANDRABOSE a Jaroslav KOČA. Selectins-The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules-A Review. \textit{Molecules}. Basel: Academic Press, 2020, roč.~25, č.~12, s.~1-61. ISSN~1420-3049. Dostupné z: https://dx.doi.org/10.3390/molecules25122835.

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