Exploring Glycan Binding Specificity of Odorranalectin by Alanine Scanning Library.

Fluorescently labelled alanine scan analogues of odorranalectin (OL), a cyclic peptide that exhibits lectin like properties, were screened for binding BSA-conjugated monosaccharides using an enzyme-linked lectin assay (ELLA). Results revealed that Lys, Phe, Tyr, Gly, Leu, and Thr were crucial for binding BSA-L-fucose, BSA-D-galactose and BSA--acetyl-D-galactosamine. Notably, Ala substitution of Ser, Pro, and Val resulted in higher binding affinities compared to the native OL.

Mucin-Type -Glycosylation Proximal to β-Secretase Cleavage Site Affects APP Processing and Aggregation Fate.

The amyloid-β precursor protein (APP) undergoes proteolysis by β- and γ-secretases to form amyloid-β peptides (Aβ), which is a hallmark of Alzheimer's disease (AD). Recent findings suggest a possible role of -glycosylation on APP's proteolytic processing and subsequent fate for AD-related pathology. We have previously reported that Tyr--glycosylation and the Swedish mutation accelerate cleavage of APP model glycopeptides by β-secretase (amyloidogenic pathway) more than α-secretase (non-amyloidogenic pathway).

Tyrosine -GalNAc Alters the Conformation and Proteolytic Susceptibility of APP Model Glycopeptides.

The amyloid-β precursor protein (APP) undergoes proteolytic cleavage by α-, β-, and γ-secretases, to determine its fate in Alzheimer's disease (AD) pathogenesis. Recent findings suggest a possible role of -glycosylation in APP's proteolytic processing. Therefore, we synthesized native and Swedish-double-mutated APP (glyco)peptides with Tyr--GalNAc.

TF-containing MUC1 glycopeptides fail to entice Galectin-1 recognition of tumor-associated Thomsen-Freidenreich (TF) antigen (CD176) in solution.

Aberrant Mucin-1 (MUC1) glycosylation with the Thomsen-Friedenreich (TF) tumor-associated antigen (CD176) is a hallmark of epithelial carcinoma progression and poor patient prognosis. Recognition of TF by glycan-binding proteins, such as galectins, enables the pathological repercussions of this glycan presentation, yet the underlying binding specificities of different members of the galectin family is a matter of continual investigation. While Galectin-3 (Gal-3) recognition of TF has been well-documented at both the cellular and molecular level, Galectin-1 (Gal-1) recognition of TF has only truly been alluded to in cell-based platforms.

Positional Scanning MUC1 Glycopeptide Library Reveals the Importance of PDTR Epitope Glycosylation for Lectin Binding.

One of the main barriers to explaining the functional significance of glycan-based changes in cancer is the natural epitope heterogeneity found on the surface of cancer cells. To help address this knowledge gap, we focused on designing synthetic tools to explore the role of tumor-associated glycans of MUC1 in the formation of metastasis via association with lectins. In this study, we have synthesized for the first time a MUC1-derived positional scanning synthetic glycopeptide combinatorial library (PS-SGCL) that vary in number and location of cancer-associated Tn antigen using the "tea bag" approach.