Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• approach by investigating the in-silico binding of a peptide and glycopeptide epitope of the glycoprotein Mucin 1 (MUC1) binding with the antibody AR20.5. To study the binding, we performed molecular dynamics simulations using OpenMM and then used the Galaxy platform for data analysis. The same analysis

• secretions and are heavily O-glycosylated [7]. Mucins serve several functions: including protecting the body from pathogens by forming chemical barriers and cellular signaling. Mucin 1 (MUC1) is tethered to the cellular membrane and is found to be aberrantly glycosylated and overexpressed in several

• epithelial cancers [8]. Further, it is thought to participate in the hyperactivation of selected intracellular signal transduction pathways that promote tumorigenicity [9]. MUC1 is a cancer biomarker that can be detected by serum biomarker assays (such as the CA15-3 test [10][11]). The mode of binding

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• example, in anti-HIV therapy, MUC1-based antitumor vaccines, or as antibiotics [12][13][14]. Especially glycans bearing noncanonical amino acids, which can only be introduced into a peptide by organic synthesis, are suitable for cancer therapy since they show better resistance to enzymatic degradation in

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• , L-ascorbic acid and applying mild heat, the desired 1,2-trans click triazole could be obtained in good to excellent yield [85]. This reaction was shown to be very robust as not only di- and oligosaccharides can be formed (one example is shown in Scheme 28B), but also cancer-associated MUC1

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• cytotoxic activity toward lymphoma cells, resulting active at a very low micromolar range [101]. With the aim to activate the human immune system against self-tumor cells, Schlecht and co-workers designed the synthesis of AuNPs functionalized with Mucin1(MUC1)-glycopeptide antigens [102]. Mucins are a

• family of glycosylated proteins with a high molecular weight, produced by epithelial tissues. The most studied is the membrane-bound glycoprotein MUC1, a glycoprotein with extensive O-linked glycosylation in its extracellular domain. The authors demonstrated that the multivalent presentation of MUC1

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• scientific community. The tumor-associated glycoprotein MUC1 represents a well-established target for cancer immunotherapy and has been used for the construction of various synthetic vaccine candidates. However, many of these vaccine prototypes suffer from an inherent low immunogenicity and are susceptible

• to rapid in vivo degradation. To overcome these drawbacks, novel fluorinated MUC1 glycopeptide-BSA/TTox conjugate vaccines have been prepared. Immunization of mice with the 4’F-TF-MUC1-TTox conjugate resulted in strong immune responses overriding the natural tolerance against MUC1 and producing

• selective IgG antibodies that are cross-reactive with native MUC1 epitopes on MCF-7 human cancer cells. Keywords: cancer immunotherapy; fluorinated carbohydrates; glycoconjugates; MUC1; TACA; Introduction Since cancer has advanced to one of the leading causes of death in economical developed countries

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• mucus. Among them, mucin 1 (MUC1) is expressed on almost all epithelial tissues. Changes of the cell-surface protein glycosylation together with MUC1 protein overexpression, results in the formation of tumor-specific epitopes consisting of both the formed short saccharides, e.g., TN, T, sialyl-TN and

• sialyl-T, and the mucin tandem repeat peptide region, which is exposed due to the aberrant glycosylation (Figure 1) [25][26][27]. A number of synthetic glycopeptide vaccines with the MUC1 tumor associated glycopeptide epitope as target have recently been prepared. Variation of glycan structure, number of

• glycans per repeat, and the sites for glycan attachment on the MUC1 peptide backbone were explored. For the induction of a strong and specific immune response, different immuno-stimulants were connected to the mucin glycopeptides. Among the immuno-stimulants, the Toll-like receptor 2 (TLR2) ligand

Synthesis of glycosylated β³-homo-threonine conjugates for mucin-like glycopeptide antigen analogues

• Florian Karch and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2010, 6, No. 47, doi:10.3762/bjoc.6.47

• amino acid tandem repeat sequence of MUC1 using sequential solid-phase glycopeptide synthesis, a first example of a mixed α/β-hybrid glycopeptide building block was obtained. The latter is of interest for the development of novel glycoconjugate mimics and model structures for anti-cancer vaccines with

• increased biological half-life. Keywords: glycopeptide; glycosylamino acids; β3-homo-threonine; MUC1 antigens; solid-phase synthesis; Introduction Glycosylation is the predominant co- and post-translational modification in higher organisms responsible for tailoring and fine-tuning of the activity of

• presenting orthogonally protected TN and TF antigen conjugates of Fmoc-β3hThr (Figure 1) as well as a first α/β-hybrid glycopeptide analogue comprising the 20 amino acid tandem repeat sequence of the human mucin MUC1, we describe preliminary results of our synthetic efforts towards the preparation of mucin