Attachment Of Chains Research Articles

Development of hydrophobic polyurethane film from structurally modified castor oil and its anticorrosive performance

AbstractHydrophobic polyurethane (PU) films are widely used for various commercial and industrial applications due to their excellent water repelling and self‐cleaning property. Nevertheless, achieving appreciable hydrophobicity in PU film is quite a challenge. Herein, we report on the development of a novel hydrophobic PU (fluorinated polyurethane [FCO‐PU]) film and comprehensively evaluate its anticorrosive property. The FCO‐PU was prepared by structural modification of castor oil (CO) through attachment of long fluorocarbon chains as pendant groups onto the backbone of CO. A model PU film (CO‐PU) was also prepared from unmodified CO to compare the properties of FCO‐PU film. All intermediate compounds, FCO‐PU and CO‐PU films were characterized by various spectroscopic techniques. Morphological, thermal and mechanical properties of the PU films were analyzed by field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical thermal analysis (DMTA) studies. Successful introduction of long fluorocarbon chains into the FCO‐PU film is reflected by its high hydrophobicity with a water contact angle of 119.1°, compared to the model CO‐PU film with a water contact angle of 84.4°. Anticorrosive properties of the PU films were evaluated by polarization technique and electrochemical impedance spectroscopy under corrosive environment and the obtained results reveal a significant corrosion resistance (corrosion rate: 6.72 × 10−6 mm/year) behavior by the FCO‐PU film. This work represents an effective strategy for the backbone modification of CO to develop novel functional PU materials.

Highly Emissive Luminogens in Both Solution and Aggregate States

Highly Emissive Luminogens in Both Solution and Aggregate States

Oligoimide-Mediated Graphene Oxide-Epoxy Nanocomposites with Enhanced Thermal Conductivity and Mechanical Properties.

The current study reports the preparation of thermally conductive polymeric nanocomposites. For this purpose, two epoxy-based nanocomposites were prepared by dispersing a different type of functionalized graphene oxide (GO) nanofiller in each series. Both these GO nanofillers were functionalized by covalently bonding oligoimide chains on their surfaces. In one series, these oligoimide chains were prepared by reaction of 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (BTDA) with a diamine 4,4′-methylenedianiline (MDA). While in the other case, BTDA was reacted with N,N′-[((propane-2,2-diylbis(4,1-phenylene))bis(oxy))bis(4,1-phenylene)]bis(4-aminobenzamide) (BDM) to mount oligoimide chains on the surface of GO. Both types of oligoimide chains have amino groups as chain-end functional groups. These modified GO nanofillers were added to the epoxy matrices separately to prepare their respective nanocomposites (MDA-B-GO-epoxy nanocomposites and BDM-B-GO-epoxy nanocomposites). The chain-end amino groups of oligoimide chains reacted with the epoxy ring developing a covalent bonding between oligoimide chains of GO and the epoxy matrix. Moreover, these oligoimide chains prevented the agglomeration of GO by acting as spacer groups leading to the uniform dispersion of GO in the epoxy matrix. Various analytical techniques were used to examine the attachment of oligoimide chains to the GO surface, and to examine the morphology, curing potential, mechanical strength, thermal stability, and thermal conductivity of the prepared nanocomposites. We demonstrated that the thermal conductivity of MDA-B-GO-epoxy nanocomposites increased by 52% and an increase of 56% was observed in BDM-B-GO-epoxy nanocomposites. Similarly, a significant improvement was observed in the mechanical strength and thermal stability of both types of nanocomposites.

A novel cytoskeletal action of xylosides.

Proteoglycan glycosaminoglycan (GAG) chains are attached to a serine residue in the protein through a linkage series of sugars, the first of which is xylose. Xylosides are chemicals which compete with the xylose at the enzyme xylosyl transferase to prevent the attachment of GAG chains to proteins. These compounds have been employed at concentrations in the millimolar range as tools to study the role of GAG chains in proteoglycan function. In the course of our studies with xylosides, we conducted a dose-response curve for xyloside actions on neural cells. To our surprise, we found that concentrations of xylosides in the nanomolar to micromolar range had major effects on cell morphology of hippocampal neurons as well as of Neuro2a cells, affecting both actin and tubulin cytoskeletal dynamics. Such effects/morphological changes were not observed with higher xyloside concentrations. We found a dose-dependent alteration of GAG secretion by Neuro2a cells; however, concentrations of xylosides which were effective in altering neuronal morphology did not cause a large change in the rate of GAG chain secretion. In contrast, both low and high concentrations of xylosides altered HS and CS composition. RNAseq of treated cells demonstrated alterations in gene expression only after treatment with millimolar concentration of xylosides that had no effect on cell morphology. These observations support a novel action of xylosides on neuronal cells.

The 26S Proteasome Switches between ATP-Dependent and -Independent Mechanisms in Response to Substrate Ubiquitination.

The ubiquitin–proteasome system is responsible for the bulk of protein degradation in eukaryotic cells. Proteins are generally targeted to the 26S proteasome through the attachment of polyubiquitin chains. Several proteins also contain ubiquitin-independent degrons (UbIDs) that allow for proteasomal targeting without the need for ubiquitination. Our laboratory previously showed that UbID substrates are less processively degraded than ubiquitinated substrates, but the mechanism underlying this difference remains unclear. We therefore designed two model substrates containing both a ubiquitination site and a UbID for a more direct comparison. We found UbID degradation to be overall less robust, with complete degradation only occurring with loosely folded substrates. UbID degradation was unaffected by the nonhydrolyzable ATP analog ATPγS, indicating that UbID degradation proceeds in an ATP-independent manner. Stabilizing substrates halted UbID degradation, indicating that the proteasome can only capture UbID substrates if they are already at least transiently unfolded, as confirmed using native-state proteolysis. The 26S proteasome therefore switches between ATP-independent weak degradation and ATP-dependent robust unfolding and degradation depending on whether or not the substrate is ubiquitinated.

The 26S Proteasome Switches Between ATP‐Dependent and Independent Mechanisms in Response to Substrate Ubiquitination

The Ubiquitin‐Proteasome System is responsible for the bulk of protein degradation in eukaryotic cells. Proteins are generally targeted to the 26S proteasome by the attachment of polyubiquitin chains. A number of proteins also contain ubiquitin‐independent degrons (UbID) that allow for proteasomal targeting without the need for ubiquitination. UbID substrates are degraded less processively than ubiquitinated substrates, but the mechanism underlying this difference remains unclear. We therefore designed two model substrates containing both a ubiquitination site and a UbID for a more direct comparison. We found UbID degradation to be overall less robust with complete degradation only occurring with relatively unstable substrates (those that were at least transiently unfolded as determined by protease sensitivity). Surprisingly, UbID degradation was unaffected by the non‐hydrolyzable ATP analog ATPγS, which halts ATP‐dependent engagement and translocation of substrates. Furthermore, ubiquitin‐dependent degradation proceeded in a strikingly similar fashion to UbID degradation in the presence of ATPγS, suggesting the 26S proteasome may have a “default” ATP‐ and ubiquitin‐independent mechanism that is capable of unfolding and degrading less‐stable proteins.

Covalent fragment-based ligand screening approaches for identification of novel ubiquitin proteasome system modulators.

Ubiquitination is a key regulatory mechanism vital for maintenance of cellular homeostasis. Protein degradation is induced by E3 ligases via attachment of ubiquitin chains to substrates. Pharmacological exploitation of this phenomenon via targeted protein degradation (TPD) can be achieved with molecular glues or bifunctional molecules facilitating the formation of ternary complexes between an E3 ligase and a given protein of interest (POI), resulting in ubiquitination of the substrate and subsequent proteolysis by the proteasome. Recently, the development of novel covalent fragment screening approaches has enabled the identification of first-in-class ligands for E3 ligases and deubiquitinases revealing so far unexplored binding sites which highlights the potential of these methods to uncover and expand druggable space for new target classes.

Functions of Glycosylation and Related Web Resources for Its Prediction.

Glycosylation involves the attachment of carbohydrate sugar chains, or glycans, onto an amino acid residue of a protein. These glycans are often branched structures and serve to modulate the function of proteins. Glycans are synthesized through a complex process of enzymatic reactions that occur in the Golgi apparatus in mammalian systems. Because there is currently no sequencer for glycans, technologies such as mass spectrometry is used to characterize glycans in a biological sample to ascertain its glycome. This is a tedious process that requires high levels of expertise and equipment. Thus, the enzymes that work on glycans, called glycogenes or glycoenzymes, have been studied to better understand glycan function. With the development of glycan-related databases and a glycan repository, bioinformatics approaches have attempted to predict the glycosylation pathway and the glycosylation sites on proteins. This chapter introduces these methods and related Web resources for understanding glycan function.

Manipulation of peptide-fatty acid bioconjugates on graphene: effects of fatty acid chain length and attachment point.

The non-destructive functionalisation of graphene in aqueous media is a critical process with the potential to enhance the versatility of the 2D nanosheet material as a technological enabler. This could also unlock strategies for a wider uptake of graphene in bio-related applications. Graphene functionalisation can be achieved using peptides that specifically recognise the carbon-based material, resulting in persistent non-covalent adsorption without damaging the nanosheet. Bio-conjugation of non-natural moieties with these peptides can incorporate multifunctionality, further extending the applicability of these interfaces. Here, bio-conjugates comprising a graphene-binding peptide with a fatty acid chain of varying length are investigated for their binding affinity and adsorbed structures at the aqueous graphene interface. Through an integration of quartz crystal microbalance and atomic force microscopy data with advanced sampling molecular simulations, variations in the binding of these bio-conjugates is determined. Conjugation at either terminus led to good interfacial contact, and for a given attachment point, the changes in the fatty acid length did not substantially disrupt the conformations of the adsorbed peptide domain. These findings provide a solid foundation for designing multi-functional bio-interfaces for sensing and healthcare.

Solid-phase synthesis of novel antimicrobial peptoids with α- and β-chiral side chains.

Bacterial resistance to conventional antibiotics poses an immense threat to human health and consequently many bacterial infections arise from multi-drug resistant pathogens. It is, therefore, necessary to continue to develop novel antimicrobials. Peptoids are a novel class of antimicrobial agents that mimic the structures of peptides. These N-substituted glycines differ from peptides in the side chain attachment site where in peptoids, the side chain functionality is introduced at the nitrogen rather than the α-carbon in peptides. During the process of design and development of antimicrobial peptoids, several key elements such as charge and amphiphilicity appear to guide peptoid bioactivity against bacterial pathogens. In this study, we report a quick synthesis of three novel cationic antimicrobial peptoids that contain charged, hydrophobic, and chiral monomers. This study is the first to use a monomer that contains both charge and chiral center for the design of the novel peptoid sequences.

The ARRE RING-Type E3 Ubiquitin Ligase Negatively Regulates Cuticular Wax Biosynthesis in Arabidopsis thaliana by Controlling ECERIFERUM1 and ECERIFERUM3 Protein Levels.

The outer epidermal cell walls of plant shoots are covered with a cuticle, a continuous lipid structure that provides protection from desiccation, UV light, pathogens, and insects. The cuticle is mostly composed of cutin and cuticular wax. Cuticular wax synthesis is synchronized with surface area expansion during plant development and is associated with plant responses to biotic and abiotic stresses. Cuticular wax deposition is tightly regulated by well-established transcriptional and post-transcriptional regulatory mechanisms, as well as post-translationally via the ubiquitin-26S proteasome system (UPS). The UPS is highly conserved in eukaryotes and involves the covalent attachment of polyubiquitin chains to the target protein by an E3 ligase, followed by the degradation of the modified protein by the 26S proteasome. A large number of E3 ligases are encoded in the Arabidopsis genome, but only a few have been implicated in the regulation of cuticular wax deposition. In this study, we have conducted an E3 ligase reverse genetic screen and identified a novel RING-type E3 ubiquitin ligase, AtARRE, which negatively regulates wax biosynthesis in Arabidopsis. Arabidopsis plants overexpressing AtARRE exhibit glossy stems and siliques, reduced fertility and fusion between aerial organs. Wax load and wax compositional analyses of AtARRE overexpressors showed that the alkane-forming branch of the wax biosynthetic pathway is affected. Co-expression of AtARRE and candidate target proteins involved in alkane formation in both Nicotiana benthamiana and stable Arabidopsis transgenic lines demonstrated that AtARRE controls the levels of wax biosynthetic enzymes ECERIFERUM1 (CER1) and ECERIFERUM3 (CER3). CER1 has also been confirmed to be a ubiquitination substrate of the AtARRE E3 ligase by an in vivo ubiquitination assay using a reconstituted Escherichia coli system. The AtARRE gene is expressed throughout the plant, with the highest expression detected in fully expanded rosette leaves and oldest stem internodes. AtARRE gene expression can also be induced by exposure to pathogens. These findings reveal that wax biosynthesis in mature plant tissues and in response to pathogen infection is controlled post-translationally.

Glycobiology of the Epithelial to Mesenchymal Transition.

Glycosylation consists in the covalent, enzyme mediated, attachment of sugar chains to proteins and lipids. A large proportion of membrane and secreted proteins are indeed glycoproteins, while glycolipids are fundamental component of cell membranes. The biosynthesis of sugar chains is mediated by glycosyltransferases, whose level of expression represents a major factor of regulation of the glycosylation process. In cancer, glycosylation undergoes profound changes, which often contribute to invasion and metastasis. Epithelial to mesenchymal transition (EMT) is a key step in metastasis formation and is intimately associated with glycosylation changes. Numerous carbohydrate structures undergo up- or down-regulation during EMT and often regulate the process. In this review, we will discuss the relationship with EMT of the N-glycans, of the different types of O-glycans, including the classical mucin-type, O-GlcNAc, O-linked fucose, O-linked mannose and of glycolipids. Finally, we will discuss the role in EMT of galectins, a major class of mammalian galactoside-binding lectins. While the expression of specific carbohydrate structures can be used as a marker of EMT and of the propensity to migrate, the manipulation of the glycosylation machinery offers new perspectives for cancer treatment through inhibition of EMT.

Elucidating the Impact of Betaglycan Glycosaminoglycan Chain Modification on Ectodomain Shedding and Cell Signaling in Ovarian Cancer

Proteoglycans (PG) are crucial components of the cell surface and extracellular matrix, acting as critical effectors of cellular homeostasis and cancer pathogenesis. Betaglycan (BG) is a ubiquitously expressed transmembrane PG containing a core protein domain with glycosaminoglycan (GAG) attachment sites at S534/S545 residues on its extracellular domain, to which heparan sulfate (HS) and chondroitin sulfate (CS) chains are covalently attached. BG is commonly referred to as a “part-time proteoglycan” since BG can be expressed on the cell surface with or without GAG chain modifications. BG's ectodomain can also be shed (shed-BG) from the cell surface to release a soluble form. BG is an established co-receptor for the TGF-β superfamily that modulates signaling of TGF-β members both at the cell surface and via the shed form as has been previously reported in breast cancer. Although majority of the prior work has focused on BG's core protein interactions and functions, a thorough understanding of the effects of the BG GAG chains remains lacking. We find in preliminary studies, elevated shed-BG in the ascites fluid of ovarian cancer (OVCA) patients compared to circulating levels in healthy individuals. Interestingly, analysis of the GAG chains on shed-BG from ascites fluid indicates majority of shed-BG in patient sample to be heavily modified with a higher degree of CS modification as compared to HS modifications on BG. Given the gap in knowledge on BG GAG chain functions and our observations in patients, I hypothesize that the GAG chains of BG may impact shedding and cell signaling that regulates ovarian cancer growth and metastasis. To examine the effect of GAG modifications on shedding of BG, we constructed point mutations at S534/S545 to abrogate GAG chain attachment sites on BG. These constructs were expressed in a panel of OVCA cell lines generating cell lines expressing either 1: Wild Type BG (BG-FL), 2: S534A (BG-CS), 3: S545A (BG-HS) or 4: S534A, S545A double mutant designated (∆GAG). Cellular expression of BG constructs confirmed the alterations in BG GAG chains. Evaluation of shedding of BG revealed a significant reduction in BG shedding from cells expressing unmodified BG (∆GAG) compared to cells expressing GAG modified BG despite no change in cell surface expression. To next evaluate the impact of expression of GAG modified BG on tumor cell biology, in vitro cell proliferation, cell invasion and migration assays were conducted. We find that both cell proliferation and invasion of BG-CS and BG-HS mutants were significantly lower as compared to BG-∆GAG mutant. These findings together suggest distinct roles for the different modified forms of BG in promoting BG shedding from the cell surface and tumor cell behavior. Additional data on the effect of BG chain modification on TGF-β, Wnt, and FGF2 signaling modulation will also be presented. Based on our findings we propose that the, GAG chains of BG regulate core protein shedding and growth factor signaling thereby impacting OVCA cell biology.

Alkyl-Fullerene Materials of Tunable Morphology and Function

Abstract The self-assembly of molecules into complex superstructures underpins the functionality of many biological processes and physical materials. Many such structures stem from amphiphilic monomer units, with attractions and repulsions between their ends determining the structure and state of the assembled system under equilibrium, which affect its function. The photophysical and electronic properties of fullerene (C60) have been extensively studied and proven useful in the fabrication of a variety of devices. The simple attachment of alkyl side chains can convert this highly crystalline solid into an alkyl-C60 hydrophobic amphiphile, in which alkyl-alkyl and C60-C60 interactions determine the state, phase, morphology, or architecture of the substance, while the optoelectronic properties of C60 are retained. In this award article, lipid membranes, crystalline nanostructures, mesophases, and even room-temperature liquid alkyl fullerenes formed through this approach are described. In each case, the effects of chain selection and substitution on morphology and function are explained. The ways in which the inherent properties of C60 can be adapted for particular applications are detailed, such as in superhydrophobic surfaces and photoconductive devices. Thereafter, drawing on these advances, the application of the alkyl chain attachment approach to other functional π-conjugated cores is demonstrated using some examples of functional molecular liquids.

Molecular modeling provides insights into the loading of sialic acid-containing antigens onto CRM197: the role of chain flexibility in conjugation efficiency and glycoconjugate architecture.

Vaccination is the most cost-effective way to control disease caused by encapsulated bacteria; the capsular polysaccharide (CPS) is the primary virulence factor and vaccine target. Neisseria meningitidis (Nm) serogroups B, C, Y and W all contain sialic acid, a common surface feature of human pathogens. Two protein-based vaccines against serogroup B infection are available for human use while four tetravalent conjugate vaccines including serogroups C, W and Y have been licensed. The tetravalent Menveo® conjugate vaccine is well-defined: a simple monomeric structure of oligosaccharides terminally conjugated to amino groups of the carrier protein CRM197. However, not only is there a surprisingly low limit for antigen chain attachment to CRM197, but different serogroup saccharides have consistently different CRM197 loading, the reasons for which are unclear. Understanding this phenomenon is important for the long-term goal of controlling conjugation to prepare conjugate vaccines of optimal immunogenicity. Here we use molecular modeling to explore whether antigen flexibility can explain the varying antigen loading of the conjugates. Because flexibility is difficult to separate from other structural factors, we focus on sialic-acid containing CPS present in current glycoconjugate vaccines: serogroups NmC, NmW and NmY. Our simulations reveal a correlation between Nm antigen flexibility (NmW > NmC > NmY) and the number of chains attached to CRM197, suggesting that increased flexibility enables accommodation of additional chains on the protein surface. Further, in silico models of the glycoconjugates confirm the relatively large hydrodynamic size of the saccharide chains and indicate steric constraints to further conjugation.

Effects of Hydrophobic Modifications on the Solution Self-Assembly of P(DMAEMA-co-QDMAEMA)-b-POEGMA Random Diblock Copolymers.

In this work, the synthesis and the aqueous solution self-assembly behavior of novel partially hydrophobically modified poly(2-(dimethylamino) ethyl methacrylate)-b-poly(oligo(ethylelene glycol) methyl ether methacrylatetabel) pH and temperature responsive random diblock copolymers (P(DMAEMA-co-Q6/12DMAEMA)-b-POEGMA), are reported. The chemical modifications were accomplished via quaternization with 1-iodohexane (Q6) and 1-iodododecane (Q12) and confirmed by 1H-NMR spectroscopy. The successful synthesis of PDMAEMA-b-POEGMA precursor block copolymers was conducted by RAFT polymerization. The partial chemical modification of the diblocks resulted in the permanent attachment of long alkyl chains on the amine groups of the PDMAEMA block and the presence of tertiary and quaternary amines randomly distributed within the PDMAEMA block. Light scattering techniques confirmed that the increased hydrophobic character results in the formation of nanoaggregates of high mass and tunable pH and temperature response. The characteristics of the aggregates are also affected by the aqueous solution preparation protocol, the nature of the quaternizing agent and the quaternization degree. The incorporation of long alkyl chains allowed the encapsulation of indomethacin within the amphiphilic diblock copolymer aggregates. Nanostructures of increased size were detected due to the encapsulation of indomethacin into the interior of the hydrophobic domains. Drug release studies demonstrated that almost 50% of the encapsulated drug can be released on demand by aid of ultrasonication.

Substituent Effects Control Spiropyran-Merocyanine Equilibria and Mechanochromic Utility.

Spiropyran (SP) derivatives can be converted into the colored merocyanine (MC) form using a variety of triggers. Optical switching by light for memories and dynamic systems is long known. Recently, mechanical force has been reported as an additional stimulus that converts SP into MC. SP-based mechanochromic systems are especially interesting for polymer scientists, as the covalent attachment of polymer chains is ideal to transduce force to the SP level. Whether such materials are investigated to better understand fundamental processes or long standing questions in polymer science, to design force sensors or to self-report damage, or simply pose fascinating materials which turn colored upon deformation, they have intrigued polymer scientists for more than a decade. With the chemistry of SPs being feasible and SP functionalization important to modulate SP/MC equilibria, a significant amount of work on SP structure- mechanochromic function relations has accumulated. SPs can be used as bifunctional initiators, cross-linkers, monomers, or be synthesized during polymerization. This feature article provides an overview of how the chemistry used sets the boundaries within which the mechanochromic response of SP containing polymers can be modulated.

What is Best Strategy for Water Soluble Fluorescence Dyes?-A Case Study Using Long Fluorescence Lifetime DAOTA Dyes*.

The lipophilic nature of organic dyes complicates their effectiveness in aqueous solutions. In this work we investigate three different strategies for achieving water-solubility of the diazaoxatriangulenium (DAOTA+ ) chromophore: hydrophilic counter ions, aromatic sulfonation of the chromophore, and attachment of charged side chains. The long fluorescence lifetime (FLT, τf =20 ns) of DAOTA+ makes it a sensitive probe to analyze solvation and aggregation effects. Direct sulfonation of the chromophore was found to increase solubility drastically, but at the cost of greatly reduced quantum yields (QYs) due to enhanced non-radiative deactivation processes. The introduction of either cationic (4) or zwitterionic side chains (5), however, brings the FLT (τf =18 ns) and QY (ϕf =0.56) of the dye to the same level as the parent chromophore in acetonitrile. Time-resolved fluorescence spectroscopy also reveals a high resistance to aggregation and non-specific binding in a high loading of bovine serum albumin (BSA). The results clearly show that addition of charged flexible side chains is preferable to direct sulfonation of the chromophore core.

Chemical Treatment of Lignosulfonates Under DBD Plasma Conditions. I. Spectral Characterization

A new method for chemical modification of lignin product under dielectric barrier discharge (DBD) plasma at atmospheric pressure is proposed. The motivation of this study is to obtain from ammonium lignosulfonate powder (ALS) and carboxylic acids (oleic acid, OA and lactic acid, LA) and butyrolactone (BL), new products with improved functionalities (ALS-LA, ALS-OA and ALS-BL), which may be used in manufacturing of biocomposite materials. The chemical transformations on the surface of ALS were evaluated by elemental analysis, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), near-infrared (NIR) spectroscopy and near-infrared chemical imaging (NIR-CI), as well as nuclear magnetic resonance (1H-NMR and 13C-NMR), UV–VIS and fluorescence spectroscopies. The attachment of the monomeric chains to the macromolecular network of ALS was proved by the values of atomic ratios (C/H, C/O and O/C), calculated from elemental analysis, reveal. The spectral results confirmed that the grafting reaction of ammonium lignosulfonate took place under cold plasma conditions and various compounds with special structures and functionalities have been obtained. Moreover, the recorded NIR-CI images (RGB and PCA components) provide information about ALS product homogeneity.

Impact of protein glycosylation on lipoprotein metabolism and atherosclerosis.

Protein glycosylation is a post-translational modification consisting in the enzymatic attachment of carbohydrate chains to specific residues of the protein sequence. Several types of glycosylation have been described, with N-glycosylation and O-glycosylation being the most common types impacting on crucial biological processes, such as protein synthesis, trafficking, localization, and function. Genetic defects in genes involved in protein glycosylation may result in altered production and activity of several proteins, with a broad range of clinical manifestations, including dyslipidaemia and atherosclerosis. A large number of apolipoproteins, lipoprotein receptors, and other proteins involved in lipoprotein metabolism are glycosylated, and alterations in their glycosylation profile are associated with changes in their expression and/or function. Rare genetic diseases and population genetics have provided additional information linking protein glycosylation to the regulation of lipoprotein metabolism.