Guanosine diphosphate-L-fucose (GDP-L-fucose)

Guanosine diphosphate-L-fucose (GDP-L-fucose) is a critical nucleotide sugar that serves as the universal donor for fucosyltransferases, enzymes responsible for adding fucose moieties to glycoproteins and glycolipids (PubChem CID 18222). This process, known as fucosylation, is essential for various biological processes, including cell-cell recognition, leukocyte extravasation via selectin ligands, and the modulation of signaling pathways such as Notch (PubMed: 30108024). In many cancers, aberrant fucosylation is observed, contributing to tumor progression, metastasis, and immune evasion (PubMed: 28614673). While GDP-L-fucose itself is a metabolite rather than a protein target, the enzymes involved in its de novo synthesis (e.g., GMDS and TSTA3) and the transporters that move it into the Golgi apparatus (e.g., SLC35C1) are significant therapeutic targets (UniProt: P35582). Small molecule inhibitors like 2-deoxy-2-fluoro-L-fucose (2FF) act by depleting the intracellular pool of GDP-L-fucose, thereby reducing global fucosylation and potentially enhancing the efficacy of other therapies like monoclonal antibodies (PubMed: 23904403). Deficiencies in the transport or synthesis of GDP-L-fucose lead to rare genetic disorders like Leukocyte Adhesion Deficiency type II (LAD II), highlighting its critical role in immune function (PubMed: 11058892).

Other names

GDP-FucGuanosine 5'-(beta-L-fucopyranosyl diphosphate)GDP-beta-L-fucose

Depletion of the intracellular GDP-L-fucose pool and competitive inhibition of fucosyltransferases (PubMed: 23904403).