Lectin Immunoassay for Macrophage-activating Factor (Gc-MAF) Produced by Deglycosylation of Gc-Globulin: Evidence for Noninducible Generation of Gc-MAF

Kanan, Raed M; Cook, David B.; Datta, Harish K.

doi:10.1093/clinchem/46.3.412

Cited by 9 publications

(2 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…K A values for interactions of HPA with groups containing terminal GalNAc range from 0.1 mM to 5 mM, within the range typical of binding of sugars to lectins [ 11 ]. HPA binds to the single O-linked α-GalNAc on the serum macrophage activating factor (GcMAF) [ 12 ]. A M13 bacteriophage library consisting of randomized 12-mer sequences at the N-terminus of the pIII protein was screened for an amino acid sequence that would bind to this lectin.…”

Section: Selection and Synthesis Of A Galnac Mimeticmentioning

confidence: 99%

A biologically active peptide mimetic of N-acetylgalactosamine/galactose

Eggink

Hoober

2009

BMC Research Notes

View full text Add to dashboard Cite

Background: Glycosylated proteins and lipids are important regulatory factors whose functions can be altered by addition or removal of sugars to the glycan structure. The glycans are recognized by sugar-binding lectins that serve as receptors on the surface of many cells and facilitate initiation of an intracellular signal that changes the properties of the cells. We identified a peptide that mimics the ligand of an N-acetylgalactosamine (GalNAc)-specific lectin and asked whether the peptide would express specific biological activity.

show abstract

Section: Selection and Synthesis Of A Galnac Mimeticmentioning

confidence: 99%

A biologically active peptide mimetic of N-acetylgalactosamine/galactose

Eggink

Hoober

2009

BMC Research Notes

View full text Add to dashboard Cite

show abstract

“…Не исключено также, что во фракции, содержащей GalNAc DBP, может присутствовать фракция белка, обладающая признаками GcMAF, но, по сути, таковой не являющаяся и не активирующая макрофаги. О такой возможности свидетельствовали тесты по связыванию лектина при отсутствии медиаторов воспаления (Kanan et al, 2000).…”

Section: является ли Gcmaf эффективным противоопухолевым препаратом?unclassified

A thorny pathway of macrophage activating factor (GcMAF): from bench to bedside

et al. 2019

View full text Add to dashboard Cite

Vitamin D3 Binding Protein (DBP) is a multifunctional glycoprotein whose main role is to transport vitamin D3 and its metabolites, but it also is the precursor of the macrophage activating factor (GcMAF). DBP is converted to GcMAF as a result of site-specific selective deglycosylation under the action of β-galactosidase and sialidase, localized on activated B and T cells, respectively. GcMAF exerts its biological activity primarily as the capability of activating macrophages by enhancing their phagocytic function and producing ROS. Activation results in elevated expression of the specific macrophageal surface receptors involved in the recognition of tumor-associated antigens, as well as in the implementation of direct anticancer activity by inducing the apoptosis or necrosis of tumor cells. Increased interest in GcMAF is associated with its potential to be used in the clinic as a new antitumor drug. Besides its anti-tumor activity, GcMAF exerts a potential against a number of viral and neurodegenerative diseases associated with increased activity of N-acetylgalactosaminidase (nagalase) in the blood serum of patients. Nagalase is an enzyme that completely (rather than selectively) deglycosylates DBP so it cannot be converted to GcMAF, leading to immunodeficiency. Circulating DBP is composed of unmodified and O-glycosylated molecules with the glycosylation degree being dependent on the allelic variants of the gene encoding DBP. The role of DBP in the resistance of organism against a number of diseases is supported by the increased risk of a variety of severe illnesses (amyotrophic lateral sclerosis, colorectal cancer etc.) in patients deficient for GcMAF due to homozygosity for defective DBP alleles. In this review, we also will examine in detail the current data i) on the structure and functions of DBP, as the main precursor of GcMAF, ii) on the main mechanisms of GcMAF anticancer effect, iii) on the tumor strategy for neutralizing GcMAF activity, iv) on the results of GcMAF clinical trials in various cancers; and will discuss the available controversies regarding the positioning of GcMAF as an effective antitumor drug.

show abstract

Glycosylation status of vitamin D binding protein in cancer patients

2009

View full text Add to dashboard Cite

On the basis of the results of activity studies, previous reports have suggested that vitamin D binding protein (DBP) is significantly or even completely deglycosylated in cancer patients, eliminating the molecular precursor of the immunologically important Gc macrophage activating factor (GcMAF), a glycosidase-derived product of DBP. The purpose of this investigation was to directly determine the relative degree of O-linked trisaccharide glycosylation of serumderived DBP in human breast, colorectal, pancreatic, and prostate cancer patients. Results obtained by electrospray ionization-based mass spectrometric immunoassay showed that there was no significant depletion of DBP trisaccharide glycosylation in the 56 cancer patients examined relative to healthy controls. These results suggest that alternative hypotheses regarding the molecular and/or structural origins of GcMAF must be considered to explain the relative inability of cancer patient serum to activate macrophages.

show abstract

Lectin Immunoassay for Macrophage-activating Factor (Gc-MAF) Produced by Deglycosylation of Gc-Globulin: Evidence for Noninducible Generation of Gc-MAF

Cited by 9 publications

References 14 publications

A biologically active peptide mimetic of N-acetylgalactosamine/galactose

A biologically active peptide mimetic of N-acetylgalactosamine/galactose

A thorny pathway of macrophage activating factor (GcMAF): from bench to bedside

Glycosylation status of vitamin D binding protein in cancer patients

Contact Info

Product

Resources

About