Fucosylation is the process of adding
fucose
Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) l ...
sugar units to a molecule. It is a type of
glycosylation
Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...
.
It is important clinically, and high levels of fucosylation have been reported in
cancer
Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
. In cancer and inflammation there are significant changes in the expression of fucosylated molecules. Therefore, antibodies and lectins that are able to recognize cancer associated fucosylated oligosaccharides have been used as tumor markers in oncology.
It is performed by
fucosyltransferase
A fucosyltransferase is an enzyme that transfers an L-fucose sugar from a GDP-fucose (guanosine diphosphate-fucose) donor substrate to an acceptor substrate. The acceptor substrate can be another sugar such as the transfer of a fucose to a core ...
enzymes.
Fucosylation has been observed in
vertebrates
Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the subphylum Vertebra ...
,
invertebrates
Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a ''spine'' or ''backbone''), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordate subphylum ...
,
plants
Plants are the eukaryotes that form the kingdom Plantae; they are predominantly photosynthetic. This means that they obtain their energy from sunlight, using chloroplasts derived from endosymbiosis with cyanobacteria to produce sugars f ...
,
bacteria
Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
, and
fungi
A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...
. It has a role in cellular adhesion and immune regulation. Fucosylation inhibition applications are being explored for a range of clinical application including some associated with sickle cell disease, rheumatoid arthritis, tumor inhibition, and chemotherapy improvements. Recent studies on
melanoma
Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
patient specimens indicated that melanoma fucosylation and fucosylated
HLA-DRB1
HLA class II histocompatibility antigen, DRB1 beta chain is a protein that in humans is encoded by the ''HLA-DRB1'' gene. DRB1 encodes the most prevalent beta subunit of HLA-DR. DRB1 alleles, especially those encoding amino acid sequence changes ...
are associated with anti-programmed cell death protein 1 (
PD1) responder status, pointing to the potential use of melanoma fucosylation as a method for
immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
patient stratification.
Moreover, it has been reported that fucosylation is an important regulator of anti-tumor immunity and
L-fucose can be used as a potent tool for increasing immunotherapy efficacy in melanoma.
Fucosylation can help with immune response when a foreign pathogen is introduced in the body. Rapid fucosylation can occur in the epithelial lining of the small intestine as a protective mechanism to support the body’s symbiotic gut bacteria. This may regulate the bacterial genes responsible for quorum sensing or virulence, thus resulting in an increased tolerance of the infection.
References
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Carbohydrate chemistry