Diane Dayoung Park

University of California, Berkeley | UCB

Peptide-based therapeutics are recognized as potent and selective molecules but are often limited by short circulating half-lives, instability towards enzymatic degradation, and immunogenicity. To address these limitations and improve their pharmacological properties, peptides are commonly modified by the covalent attachment of polyethylene glycol...

Secreted proteins are overexpressed in cholangiocarcinoma (CCA) and actively involved in promoting metastatic spread. Many of these proteins possess one or more sites of glycosylation and their various glycoforms have potential utility as prognostic or diagnostic biomarkers. To evaluate the effects of secretome glycosylation on patient outcome, we...

Mass spectrometry-based glycome analysis is a viable strategy for the compositional and functional exploration of glycosylation. However, the lack of generic tools for high-throughput and reliable glycan spectral interpretation largely hampers the broad usability of glycomic research. Here, we developed a generic and reliable glycomic tool, GlycoNo...

We have recently introduced multiple reaction monitoring (MRM) mass spectrometry as a novel tool for glycan biomarker research and discovery. Herein, we employ this technique to characterize the site-specific glycan alterations associated with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Glycopeptides associated with di...

Events mediated by the P-selectin/PSGL-1 pathway play a critical role in the initiation and propagation of venous thrombosis by facilitating the accumulation of leukocytes and platelets within the growing thrombus. Activated platelets and endothelium both express P-selectin, which binds PSGL-1 expressed on the surface of all leukocytes. We develope...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The pleiotropic functions of macrophages in immune defense, tissue repair, and maintenance of tissue homeostasis are supported by the heterogeneity in macrophage sub-populations that differ both in ontogeny and polarization. Although glycans and glycan-binding proteins (GBPs) are integral to macrophage function and may contribute to macrophage dive...

Alterations in the human glycome have been associated with cancer and autoimmunity. Thus, constructing a site-specific map of the human glycome for biomarker research and discovery has been a highly sought-after objective. However, due to analytical barriers, comprehensive site-specific glycoprofiling is difficult to perform. To develop a platform...

Polysaccharides are the most abundant biomolecules in nature, but are the least understood in terms of their chemical structures and biological functions. Polysaccharides cannot be simply sequenced because they are often highly branched and lack a uniform structure. Furthermore, large polymeric structures cannot be directly analyzed by mass spectro...

Significance Cells assemble a dense layer composed of glycans on the plasma membrane, following nontemplated processes that can be perturbed during malignancy. The intrinsic heterogeneity of glycosylation presents challenges to unambiguously identifying disease-specific transformations and selectively targeting them while preventing off-target even...

Aryl hydrocarbon receptor (AHR) is an essential regulator of gut immunity and a promising therapeutic target for inflammatory bowel disease (IBD). Current AHR agonists are inadequate for clinical translation due to low activity, inadequate pharmacokinetics, or toxicity. We synthesized a structurally diverse library and used integrated computational...

Cell membrane protein glycosylation is dependent on the metabolic state of the cell as well as exogenous nutrients available. Although the metabolism and interconversion of monosaccharides have been well-studied, their incorporation into cell surface glycans and their corresponding glycoproteins remains relatively unknown. In this study, we develop...

Table S1. List of identified OGPs in CCA cells.

Fig. S1. Identification of O‐GlcNAcylated proteins using Click‐iT™O‐GlcNAc Enzymatic Labeling System and mass spectrometry. Fig. S2. Predicted O‐GlcNAcylated proteins in CCA cells. Fig. S3. Cell proliferation during migration and invasion assays. Fig. S4. Effect of hnRNP‐K and O‐GlcNAcylation on cell migration. Fig. S5. Expression and localizat...

O‐GlcNAcylation is a key post‐translational modification that modifies the functions of proteins. Associations between O‐GlcNAcylation, shorter survival of cholangiocarcinoma (CCA) patients and increased migration/invasion of CCA cell lines have been reported. However, the specific O‐GlcNAcylated proteins (OGPs) that participate in promotion of CCA...

The leading cause of death in cancer patients is metastasis, for which an effective treatment is still necessary. During metastasis, cancer cells aberrantly express several glycans that are correlated with poor patient outcome. This study was aimed toward exploring the effects of O-GlcNAcylation on membranous N-glycans that are associated with the...

Glycosphingolipids (GSLs) are found in cellular membranes of most organisms and play important roles in cell-cell recognition, signaling, growth, and adhesion, among others. A method based on nanoflow high performance liquid chromatography-chip-quadrupole-time-of-flight mass spectrometry (nanoHPLC Chip-Q-TOF MS) was applied towards identifying and...

Video S1. Three-dimensional Structure of Integrin β1, Highlighting the Glycosylated Residues, Related to Figures 2 and 4 A still image of Video S1 is included in this pdf

Video S2. Simulation of Integrin β1 with an N-Glycan without Core Fucosylation, Related to Figure 4 A still image of Video S1 is included in this pdf

Video S3. Simulation of Integrin β1 with an N-Glycan with Core Fucosylation, Related to Figure 4 A still image of Video S1 is included in this pdf

Table S1. Multiple Reaction Monitoring Approach for Glycoprotein Analysis, Related to Figure 1

Since hundreds of clinical trials are investigating the use of multipotent stromal cells (MSCs) for therapeutic purposes, effective delivery of the cells to target tissues is critical. We have found an unexplored mechanism, by which basic fibroblast growth factor (FGF2) induces expression of fucosyltransferase 8 (FUT8) to increase core fucosylation...

Given that unnatural sugar expression is metabolically achieved, the kinetics and disposition of incorporation can lend insight into the temporal and localization preferences of sialylation across the cell surface. However, common detection schemes lack the ability to detail the molecular diversity and distribution of target moieties. Here we emplo...

Streptococcus gordonii and Streptococcus sanguinis are typically found among the normal oral microbiota, but can also cause infective endocarditis. These organisms express cell-surface serine-rich repeat adhesins containing "Siglec-like" binding regions (SLBRs) that mediate attachment to α2-3 linked sialic acids on human glycoproteins. Two known re...

Lewis(X) (Le(X)) is a branched trisaccharide Galβ1→4(Fucα1→3)GlcNAc that is expressed on many cell surface glycoproteins and plays critical roles in innate and adaptive immune responses. However, efficient synthesis of glycopeptides bearing Le(X) remains a major limitation for structure-function studies of the Le(X) determinant. Here we report a to...

Epithelial cells in the lining of the intestines play critical roles in maintaining homeostasis while challenged by dynamic and sudden changes in luminal contents. Given the high density of glycosylation that encompasses their extracellular surface, environmental changes may lead to extensive reorganization of membrane-associated glycans. However,...

Although gut host-pathogen interactions are glycan-mediated processes, few details are known about the participating structures. Here we employ high-resolution mass spectrometric profiling to comprehensively identify and quantitatively measure the exact modifications of native intestinal epithelial cell surface N-glycans induced by S. Typhimurium i...

Protein glycosylation and other post-translational modifications are involved in potentially all aspects of human growth and development. Defective glycosylation has adverse effects on human physiological conditions and accompanies many chronic and infectious diseases. Altered glycosylation can occur at the onset and/or during tumor progression. Id...

A new acridone derivative 2-aminoacetamido-10-(3, 5-dimethoxy)-benzyl-9(10H)-acridone hydrochloride (8a) has been shown to have potent antitumor activity. In order to understand the underlying action mechanism of 8a, three compounds of the same class with structures optimized step-by-step, 9(10H)-acridone (A), 10-(3,5-dimethoxy) benzyl-9(10H)-acrid...

Complex glycans cover the gut epithelial surface to protect the cell from the environment. Invasive pathogens must breach the glycan layer before initiating infection. While glycan degradation is crucial for infection, this process is inadequately understood. Salmonella contains 47 glycosyl hydrolases (GHs) that may degrade the glycan. We hypothesi...

During the development of recombinant monoclonal antibody (rMAb) drugs, glycosylation receives particular focus because changes in the attached glycans can have a significant impact on the antibody effector functions. The vast heterogeneity of structures that exist across glycosylation sites hinders the in-depth analysis of glycan changes specific...

Changes in cell surface glycosylation occur during the development and differentiation of cells and have been widely correlated with the progression of several diseases. Due to their structural diversity and sensitivity to intra- and extracellular conditions, glycans are an indispensable tool for analyzing cellular transformations. Glycans present...

Photofragment translational spectroscopy was used to study the photodissociation of the methyl perthiyl radical CH(3)SS at 248 nm. The radical was produced by flash pyrolysis of dimethyl disulfide (CH(3)SSCH(3)). Two channels were observed: CH(3) + S(2) and CH(2)S + SH. Photofragment translational energy distributions indicate that CH(3) + S(2) res...

The collisionless photodissociation dynamics of isobutene (i-C(4)H(8)) at 193 nm via photofragment translational spectroscopy are reported. Two major photodissociation channels were identified: H + C(4)H(7) and CH(3) + CH(3)CCH(2). Translational energy distributions indicate that both channels result from statistical decay on the ground state surfa...

The photodissociation dynamics of the tert-butyl radical (t-C(4)H(9)) were investigated using photofragment translational spectroscopy. The tert-butyl radical was produced from flash pyrolysis of azo-tert-butane and dissociated at 248 nm. Two distinct channels of approximately equal importance were identified: dissociation to H + 2-methylpropene, a...

Photofragment translational spectroscopy was used to study the photodissociation dynamics of the phenyl radical C(6)H(5) at 248 and 193 nm. At 248 nm, the only dissociation products observed were from H atom loss, attributed primarily to H+o-C(6)H(4) (ortho-benzyne). The observed translational energy distribution was consistent with statistical dec...