Calorimetric Analysis of the Interplay between Synthetic Tn Antigen-Presenting MUC1 Glycopeptides and Human Macrophage Galactose-Type Lectin. 2021

Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science, Florida Atlantic University, Boca Raton, Florida 33431, United States.

Human macrophage galactose-type lectin (hMGL, HML, CD301, CLEC10A), a C-type lectin expressed by dendritic cells and macrophages, is a receptor for N-acetylgalactosamine α-linked to serine/threonine residues (Tn antigen, CD175) and its α2,6-sialylated derivative (sTn, CD175s). Because these two epitopes are among malignant cell glycan displays, particularly when presented by mucin-1 (MUC1), assessing the influence of the site and frequency of glycosylation on lectin recognition will identify determinants governing this interplay. Thus, chemical synthesis of the tandem-repeat O-glycan acceptor region of MUC1 and site-specific threonine glycosylation in all permutations were carried out. Isothermal titration calorimetry (ITC) analysis of the binding of hMGL to this library of MUC1 glycopeptides revealed an enthalpy-driven process and an affinity enhancement of an order of magnitude with an increasing glycan count from 6-8 μM for monoglycosylated peptides to 0.6 μM for triglycosylated peptide. ITC measurements performed in D2O permitted further exploration of the solvation dynamics during binding. A shift in enthalpy-entropy compensation and contact position-specific effects with the likely involvement of the peptide surroundings were detected. KinITC analysis revealed a prolonged lifetime of the lectin-glycan complex with increasing glycan valency and with a change in the solvent to D2O.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002151 Calorimetry The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D005690 Galactose An aldohexose that occurs naturally in the D-form in lactose, cerebrosides, gangliosides, and mucoproteins. Deficiency of galactosyl-1-phosphate uridyltransferase (GALACTOSE-1-PHOSPHATE URIDYL-TRANSFERASE DEFICIENCY DISEASE) causes an error in galactose metabolism called GALACTOSEMIA, resulting in elevations of galactose in the blood. D-Galactose,Galactopyranose,Galactopyranoside,D Galactose
D006020 Glycopeptides Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight. Glycopeptide
D006031 Glycosylation The synthetic chemistry reaction or enzymatic reaction of adding carbohydrate or glycosyl groups. GLYCOSYLTRANSFERASES carry out the enzymatic glycosylation reactions. The spontaneous, non-enzymatic attachment of reducing sugars to free amino groups in proteins, lipids, or nucleic acids is called GLYCATION (see MAILLARD REACTION). Protein Glycosylation,Glycosylation, Protein
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000939 Epitopes Sites on an antigen that interact with specific antibodies. Antigenic Determinant,Antigenic Determinants,Antigenic Specificity,Epitope,Determinant, Antigenic,Determinants, Antigenic,Specificity, Antigenic
D015295 Antigens, Tumor-Associated, Carbohydrate Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies. Antigens, Carbohydrate, Tumor-Associated,CA Antigens,Cancer-Associated Carbohydrate Antigens,Carbohydrate Antigens, Tumor-Associated,Tumor-Associated Carbohydrate Antigens,Antigen, Carcinoma-Associated,CA Antigen,CA(Oxford) Antigen,Carcinoma-Associated Antigen,Epitectin,Antigen, CA,Antigen, Carcinoma Associated,Antigens, CA,Antigens, Cancer-Associated Carbohydrate,Antigens, Tumor-Associated Carbohydrate,Cancer Associated Carbohydrate Antigens,Carbohydrate Antigens, Cancer-Associated,Carbohydrate Antigens, Tumor Associated,Carcinoma Associated Antigen,Tumor Associated Carbohydrate Antigens

Related Publications

Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
January 2022, Molecular pharmaceutics,
Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
November 2017, Journal of medicinal chemistry,
Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
December 2023, Glycobiology,
Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
May 2021, Biochemistry,
Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
September 2023, The Journal of investigative dermatology,
Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
October 2021, Cancer letters,
Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
September 2007, Cancer research,
Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
January 2015, PloS one,
Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
September 2008, Journal of immunology (Baltimore, Md. : 1950),
Donella M Beckwith, and Forrest G FitzGerald, and Maria C Rodriguez Benavente, and Elizabeth R Mercer, and Anna-Kristin Ludwig, and Malwina Michalak, and Herbert Kaltner, and Jürgen Kopitz, and Hans-Joachim Gabius, and Maré Cudic
February 2000, The journal of peptide research : official journal of the American Peptide Society,
Copied contents to your clipboard!