| CAT# | Product Name | M.W | Molecular Formula | Inquiry |
|---|---|---|---|---|
| G21001 | α-Gliadin (31-43) | 1527.8 | ||
| G21002 | α9-Gliadin (57-68) | 1455.8 | ||
| G21003 | MUC5AC-13 | 1704.9 | ||
| G21004 | Gliadin p31-43 | 1527.7 | C71H102N18O20 |
Glycopeptides are peptides that contain one or more covalently linked carbohydrates made of l-and/or d-amino acids.Glycopeptides include the significant nonribosomally produced glycopeptides,like vancomycin and bleomycin.Last resort medications in the form of glycopeptide antibiotics provide treatment for life-threatening Gram-positive bacterial infections.Glycopeptides inhibit growth by blocking cell wall biosynthesis.They act by sequestering lipid II from the bacterial enzymes through binding.
A glycopeptide consists of a peptide structure to which one or multiple glycans have been chemically linked.The stereochemistry of the glycan and the enzymes that catalyze the glycan-peptide linkage impart physicochemical and biological properties to the glycopeptide.In N-linked glycopeptides,an oligosaccharide is attached to the peptide backbone at an Asn residue through aβ-N-glycosidic linkage.Glycosylation of Tyr,Hydroxylysine and Pro side-chains forms O-linked glycopeptides.C-linked glycopeptides are even rarer.A C–C linkage joins the C-2 atom of mannose and the C-2 atom of the indole ring of tryptophan.Structural diversity is further added by peptide backbone that can be linear or cyclic(e.g.,in glycopeptide antibiotics like vancomycin).In many glycopeptides,the glycosylation site is a loop orβ-turn that can accommodate bulky glycan groups and is often on the surface of proteins,where they mediate protein-protein interactions.Site occupancy and glycan structure may be variable(microheterogeneity)to contribute to combinatorial complexity and determine solubility,protease stability and binding.
Immunomodulatory activity of GlycopeptidesGlycopeptides can influence the immune system by multiple mechanisms and multiple targets.The most common methods for evaluating the immunomodulatory effects of glycopeptides are the detection of immune organ index,cytokine and immunoglobulin levels.Glycopeptides can slow down aging by inhibiting the degeneration of immune organs.Acidic-polysaccharide-linked glycopeptide(APGP),isolated from Korean ginseng,has been found to improve the weight and area of thymus and inhibit immune organs degeneration in the aged mice.Furthermore,APGP has been found to upregulate the number of NK cells and downregulate the number of age-related CD11c-positive B cells in spleens of the aged mice.The administration of Ganoderma lucidum polysaccharide peptide(GLPP)caused a significant decrease in CTX-induced immune injury,as revealed by immune organ index,earlap swelling rate,index of carbon phagocytosis and clearance value,secretion of cytokines(tumor necrosis factor(TNF)-α,IFN-γand IL-2)and immunoglobulin A(IgA)in mice.Yolk glycopeptide 40(YGP40)from hen egg has been found to promote TNF-αand IL-10 production and induce nitric oxide production in human whole blood cells.
Anti-inflammatory effectsLycium barbarum glycopeptide(LbGP)was found to avert acute colitis in mice through regulating the community and diversity of the intestinal microbiota.The mucus layer in the colon is vital in preserving intestinal barrier and immune homeostasis.Muc2,one of mucin expressed by intestinal epithelial cells,is a principal component of intestinal mucus layer.LbGP markedly restored colon length,inhibited the expression of glucocorticoid receptor-1(Gr-1),restored the secretion of mucus,reduced the levels of pro-inflammatory cytokines IL-1βand IL-6,increased the anti-inflammatory cytokine IL-10,and alleviated the inflammation in mice with colitis.LbGP inhibited the overgrowth of harmful bacterial flora.LbGp can avert the severe inflammatory response by regulating the phenotype of macrophages and blocking NF-κB signal transduction,and this may be due to its complex polymer structure or some other specific properties of LbGp.It has been proved that LbGp can inhibit the activation of NF-κB induced by LPS stimulation,along with the significant decrease in IL-6 and TNF-αand the increase in IL-10 and IL-4 expression,to exert the immunomodulatory function and inhibit the excessive inflammation.
Antitumor effectsGlycopeptides have been demonstrated to suppress tumor formation in vivo and in vitro.It can block apoptosis,cell cycle and affect JNK/ERK-MAPK signaling pathway.Glycopeptides may also cause intracellular reactive oxygen species to rise to toxic levels in tumor cells,thus activating ROS-induced apoptosis and cell cycle block.LbGp has been shown to induce B16 mice apoptosis,increased reactive oxygen species content in tumor cells,activate P38-MAPK signal transduction pathway,reduced p-p38,p-AKT,caspase-3,Bcl-2,cyclin D1,CDK2 proteins.LbGP was found to maintain the phosphorylation level of the AKT signaling pathway and make cells go into the state of cell cycle arrest.Lycium barbarum active glycopeptide(LBAG)can up-regulate p21 expression,down-regulate CDK2 and cell Cyclin D1 expression,and finally make B16 cell cycle arrest in G0/G1 phase.
Neuroprotective effectsGlycopeptides have neuroprotective effects and can prevent and delay Alzheimer's disease.Therefore,anti-AD that interferes with the production and aggregation of Aβis a potential therapeutic strategy.APP is successively cleaved byβ-secretase andγ-secretase to generate sAPPβ,Aβand activation induced cell death(AICD).Glycopeptide from Fructus Mori fruit can also inhibit the secretion ofβ-secretase and inhibit the expression ofγ-secretase's major component presenilin 1 to decrease Aβproduction and aggregation to achieve the neuroprotective effect.In vivo,LbGp inhibits MAPK-NF-κB and focal death-related pathways,makes microglia secrete docosahexaenoic acid(DHA)to promote neural regeneration and repair of motor function,improve inflammatory microenvironment of spinal cord injury and promote spinal cord repair,and provides a new idea for the treatment of spinal cord injury.At the same time,LbGp inhibits SCI focal death by regulating the unsaturated fatty acid DHA.Long-term oral administration of LbGp reduced anxiety and depression and protected neuronal dendrites and spinal columns in the medial prefrontal cortex(MPFC).
Other functionsEndogenous glycopeptides are present in many secretory proteins such as hormones,enzymes,and antibodies.The circulating half-life of glycoproteins is under the control of glycans.Glycans shield the peptide backbone from proteolysis and mediate clearance via mannose or asialoglycoprotein receptor.Aberrant glycosylation has been found in a variety of diseases.Congenital muscular dystrophy produces basement membrane assembly disorder when glycosylated dystroglycan is lost and hyper-sialylated tumor-associated glycopeptides increase metastasis by binding vascular endothelium expressed selectins.
An oligosaccharide's terminal N-acetylglucosamine attaches through a glycosidic bond to theδ-amide nitrogen of an Asn residue within an Asn-X-Ser/Thr sequon where X represents any amino acid but Pro.N-linked glycopeptides are produced after the oligosaccharyltransferase(OST)complex in the endoplasmic reticulum(ER)catalyzes the transfer of a preassembled 14-sugar dolichol-linked precursor en bloc onto asparagine residues of polypeptide chains as they are synthesized and enter the ER lumen.The combined actions of ERα-glucosidase trimming and Golgi glycosyltransferase remodeling give rise to the three major N-glycan classes(high-mannose,complex and hybrid),which receive distinct structures via terminal extensions and branching patterns.The core pentasaccharide maintains structural conservation across eukaryotic cells yet the addition of galactose,fucose and sialic acid residues creates microheterogeneity which affects properties like solubility,thermal stability and protease resistance.
Serine or threonine hydroxyl oxygen reacts with glycans to create O-linked glycopeptides.Sometimes,tyrosine,hydroxylysine or hydroxyproline are also involved.O-glycosylation occurs post-translationally rather than co-translationally and targets specific sites.O-glycosylation starts in the Golgi apparatus by the action of polypeptide N-acetylgalactosaminyltransferases(ppGalNAc-Ts)that transfer the firstα-GalNAc residue onto serine or threonine to generate the highly prevalent"Tn"antigen.Galactose,GlcNAc,fucose and sialic acid are added to the priming sugar by glycosyltransferases to yield mucin-type glycans with 8 different core structures that decorate epithelial secretions and membrane glycoproteins.The lack of a common sequon for O-glycosylation requires experimental mapping using tandem mass spectrometry.Current workflows such as O-Pair Search use empirical scoring to group O-glycopeptide identifications into Localization Levels(1–3)that are inversely proportional to the probability of exact glycosite assignment.O-glycopeptide mimetics are being explored as cancer vaccines to generate T-cell reactivity against cancer-specific,aberrantly glycosylated antigens.
A less common but more chemically stable class is that of C-linked glycopeptides,in which a C–C linkage attaches a mannose residue to the C-2 atom of the indole ring of a tryptophan(Trp)residue in a process called C-mannosylation.The enzyme responsible is a dedicated C-mannosyltransferase(dPYM),which targets the consensus sequence Trp-X-X-Trp/Cys in the ER lumen without a dolichol carrier.The C-mannosyltryptophan bond is chemically and enzymatically stable,making the glycopeptide highly stable.Although so far only a few proteins have been identified with C-mannosylation,including the thrombospondin type-1 repeat(TSR)domains of properdin,interleukin-12,and the complement regulator CD55,this modification is required for correct folding and secretion.
High-mannose glycopeptides contain an N-glycan with mannose residues exclusively attached to the core GlcNAc2 backbone leading to structures Man5GlcNAc2 through Man9GlcNAc2.ER-residentα-mannosidases remove the terminal glucose residues from dolichol-linked precursor glycans and Golgi glycosyltransferases do not further modify these structures.Because high-mannose glycans are substrates for endomannosidase and ERManI,high mannose glycans also connect their degradation to ER-associated glycoprotein quality control.Due to the small size of high mannose glycans,both the coreα1→3 andα1→6 mannose branches are accessible,making high mannose glycopeptides high affinity ligands for mannose binding lectins like DC-SIGN and MBL,which has made them interesting tools for HIV-1 vaccine applications.Structural analysis shows that dense clusters of mannoses on recombinant gp120 trimers induce broadly neutralizing antibodies(bnAbs)like 2G12,which has its Fab arms reoriented specifically to recognize the terminal Manα1→2Man epitope in a multivalent interaction.In monoclonal antibody therapeutics,high-mannose glycopeptides lead to decreased thermal stability,enhanced systemic clearance through the mannose receptor,and decreased complement-dependent cytotoxicity.Quantitative glycoproteomics using Endo-S/Endo-F3 release and LC-MS/MS analysis has shown that up to 14%of N-glycopeptides in total at particular sites on recombinant spike RBD produced in human HEK293 cells are high mannose species,which are generally less susceptible to fucosylation.
Complex-type glycopeptides have N-glycans with the core Man3GlcNAc2 structure elaborated by the Golgi-resident glycosyltransferases to form complex branched multi-antennary glycans terminated with galactose,N-acetylglucosamine,fucose and sialic acid(NeuAc).Biantennary complex glycans undergo modification for tri-and tetra-antennary forms with GlcNAcβ1→4 linkage and core-fucosylation on GlcNAcα1→6 linkage GlcNAc.Each of these decorations is attached to or removed from the glycan by a specific enzyme,and this combination of possible modifications underlies much of biological specificity.Terminal modifications bestow physicochemical attributes critical for in vivo performance:sialylation extends protein half-life through galactose masking to prevent asialoglycoprotein receptor binding andα2→6-linked sialic acid on respiratory tract glycoproteins serve as the main receptor for influenza A hemagglutinin.In contrast,core fucosylation dramatically weakens ADCC by reducing affinity to FcγRIIIa,a challenge that has been solved by the introduction of afucosylated therapeutic antibodies such as obinutuzumab.LC-MS/MS analysis of recombinant ACE2 and spike glycoproteins indeed revealed that N-glycopeptides are enriched in complex-type glycans(≥90%),45%of which are core-fucosylated and 21%mono-sialylated.Cancer biomarkers encompass abnormal glycan branching and increased fucosylation exemplified by the FDA-approved blood test AFP-L3 which uses core-fucosylated proteins for early detection of hepatocellular carcinoma and reflects FUT8 enzyme upregulation.
Hybrid-type glycopeptides are chimeric structures of high-mannose and complex type glycans on a single N-glycan.The Man(α1→6)arm preserves the high-mannose terminal mannose residues while the Man(α1→3)arm is elongated by GlcNAc-initiated antennae that can be further elaborated by galactose,fucose,and sialic acid.This double identity is the result of incomplete processing by mannosidases and early termination of trimming by the opposing GlcNAc-transferases(e.g.,MGAT1),leading to the formation of GlcNAcMan5GlcNAc2 or NeuAcGalGlcNAcMan4GlcNAc2.Hybrid glycopeptides are commonly found in recombinant glycoproteins expressed at high-yield where the transit time through the Golgi is limited.Their abundance is often a tell-tale sign of glycoengineering to fine-tune effector functions.Biophysically,the hybrid architecture leads to intermediate hydrodynamic radii between compact and extended high-mannose and complex species,thereby affecting protein conformational entropy and avidity.Glycoproteomic analysis of SARS-CoV-2 spike S2 subunit showed 5%of the N-glycopeptides at Asn603,Asn709,and Asn717 were of hybrid-type,with mannosidase-resistant Man₅cores juxtaposed with sialylated lactosamine antennae.These glycans are sensitive markers of host-cell glycosylation potential and are currently being explored as quality-control attributes for next generation viral-vector and subunit vaccines.
Synthetic glycopeptides consist of chemically constructed molecules combining an exact carbohydrate structure with a logically planned peptide backbone.They are synthesized only by solid-phase peptide synthesis(SPPS),native chemical ligation(NCL)or expressed protein ligation(EPL),methods that provide atomically precise control over the peptide sequence and over the site,stereochemistry and density of glycosylation.This makes synthetic glycopeptides powerful tools for understanding structure–activity relationships(SAR)of therapeutic proteins,for producing homogeneous vaccine antigens and for building glycomimetic inhibitors of lectin–glycan interactions.A recent highlight is the total synthesis of the 111-residueβ-subunit of human follicle-stimulating hormone(hFSH)with two defined complex-type N-glycans,which showed that core fucosylation and terminal sialylation are critical for full agonist activity at the FSH receptor.In another example outside reproductive biology,synthetic glycopeptide libraries were used to define the glycan specificity of HIV-1 broadly neutralizing antibodies,to permit the iterative optimization of immunogens capable of eliciting protective responses.
Natural glycopeptides are secondary metabolites,primarily made by actinomycetes(Amycolatopsis,Streptomyces,and Nonomuraea spp.)using non-ribosomal peptide synthetase(NRPS)mega-enzyme assembly lines.The prototype is vancomycin,a heptapeptide backbone that is extensively cross-linked by P450-mediated oxidative cyclizations and further elaborated with vancosamine and glucose to produce the final glycopeptide antibiotic.Natural glycopeptides bind to the D-Ala-D-Ala terminus of lipid II in Gram-positive bacteria to prevent peptidoglycan cross-linking and act as bactericidal agents.Because of their in vivo efficacy,natural glycopeptides are often used as drugs of last resort to treat MRSA and vancomycin-resistant enterococci(VRE);however,the clinical onset of vanA-type resistance to these drugs has led to the development of semi-synthetic successors(dalbavancin and oritavancin).Biosynthetic gene clusters for glycopeptide antibiotics commonly encode self-resistance cassettes that serve as a genetic reservoir from which pathogenic bacteria can acquire resistance determinants.
Recombinant glycopeptides can be synthesized in modified eukaryotic or prokaryotic expression platforms that are co-engineered to express the protein-of-interest and necessary glycosyltransferase machinery to permit true post-translational protein glycosylation.Mammalian host cells(CHO,HEK293,etc.)are best suited for the production of complex-type N-glycans that terminate in sialic acid and core fucose residues,while plant or insect expression hosts will often result in glycoforms that are exclusively high-mannose or paucimannose in structure.Site-resolved LC-MS/MS glycoproteomics of recombinant SARS-CoV-2 spike and ACE2 receptor proteins have been used to identify 148 N-glycopeptides and 28 O-glycopeptides,and has highlighted that distribution of glycoforms produced is highly sensitive to the host cell line.Alteration of the expression host's glycosylation machinery is possible(i.e.CRISPR knockout of fucosyltransferases or over-expression of sialyltransferases)to improve a glycoprotein's pharmacokinetic and protein receptor binding properties,or to otherwise reduce immunogenicity,such as afucosylated anti-CD20 antibodies with increased ADCC,or hyper-sialylated erythropoietin analogues with improved circulatory half-life.
The glycopeptides are a class of clinically crucial natural or semi-synthetic glycosylated peptides that act on Gram-positive bacteria by disrupting the late steps of peptidoglycan synthesis.The prototypical member vancomycin binds with femtomolar affinity to the d-Ala-d-Ala terminus of the peptidoglycan precursor lipid II and sterically hinders transglycosylation and transpeptidation reactions leading to cell-wall cross-linking.This explains its bactericidal activity against methicillin-resistant Staphylococcus aureus(MRSA),penicillin-resistant Streptococcus pneumoniae and susceptible enterococci.A number of"next-generation"lipoglycopeptides(teicoplanin,dalbavancin,oritavancin,telavancin)maintain this D-Ala-D-Ala recognition motif,but with additional pharmacophores for membrane-anchoring and/or membrane-depolarization.The C10 acyl chain of teicoplanin inserts into the bacterial membrane,sequestering the glycopeptide near the lipid II target,whereas telavancin causes rapid ATP and K+leakage through membrane disruption,leading to dose-dependent bactericidal kinetics.Resistance can develop by acquisition of van operons that alter the peptidoglycan precursor to terminate with d-Ala-d-Lac,instead of d-Ala-d-Ala,~1000-fold reducing its binding affinity.Antibiotic glycopeptides are now last-line drugs of choice only for life-threatening infections that are unresponsive toβ-lactams.Pharmacokinetic modifications(i.e.,dalbavancin's new once-weekly dosing regimen)aim to maintain their clinical utility while minimizing nephrotoxicity and ototoxicity of vancomycin.
Antigenic Glycopeptides
Antigenic glycopeptides are glycoconjugates designed or naturally occurring that display carbohydrate antigens in a peptide framework for the purpose of eliciting or detecting antigen-specific immune responses.Synthetic glycopeptides containing tumor-associated carbohydrate antigens(TACAs),like Tn(GalNAcα1-O-Ser/Thr)or sTn(Neu5Acα2-6GalNAcα1-O-Ser/Thr),are strong immunogens upon conjugation to carrier proteins or liposomal nanoparticles and are able to overcome B-cell tolerance to induce high-affinity IgG antibodies.HIV-1 envelope glycopeptide mimetics presenting high-mannose clusters(Man8-9GlcNAc2)are used to steer the germline precursors of broadly neutralizing antibodies(bnAbs)to mature paratopes that specifically target conserved glycan shields on gp120.In addition to their use for active immunization,antigenic glycopeptides are also used as reagents for serodiagnosis.For example,synthetic peptides modified with Asn-X-Ser sequons and core-fucosylated complex-type N-glycans are chemically immobilized in arrays to profile anti-glycan autoantibodies in rheumatoid arthritis and systemic lupus erythematosus.The defined orientation of glycans on peptide backbones facilitates multiplexed and high-throughput detection of disease-specific antibody signatures which can be used for early diagnosis and monitoring of drug efficacy.
Analytical/Standard Glycopeptides
Well-defined reference glycopeptides,also called analytical or standard glycopeptides,are highly characterized reference materials used as internal standards,positive controls and retention-time locks in LC-MS analytical glycoproteomic workflows for the purpose of glycoproteomic quantitation.Such standards are generally prepared by solid-phase peptide synthesis followed by chemoselective glycosylation and modified with stable-isotope labels(13C,15N)and site-specific glycans of known composition(Man5GlcNAc2,complex bi-antennary,sialylated tri-antennary etc.)that support isotope dilution-based absolute quantification.When validating quantitative methods,isotopically labeled glycopeptides are added to the biological matrix before tryptic digestion to account for matrix effects and variations in ionization efficiencies,in-source fragmentation and loss of recovery.For example,the glycopeptide standard 13C6-Asn42-CTLA-4-Fc with core-fucosylated biantennary glycans is commonly used to serve as a reference standard to assess site-specific glycosylation occupancy of therapeutic monoclonal antibodies.Chromatographic retention-time libraries built with synthetic glycopeptide standards are also used to support automated glycan identification in data-independent acquisition(DIA)workflows and to improve throughput and reproducibility in regulated biopharmaceutical settings.
Chemoenzymatically Synthesized Glycopeptides
Chemoenzymatic synthesis takes advantage of the regio-and stereoselectivity of glycosyltransferases or endoglycosidases and combines it with the versatility of chemical peptide assembly.This approach allows for the preparation of homogeneous glycopeptides that are often unobtainable from natural sources.The synthetic workflow generally starts from a chemically synthesized or recombinant peptide fragment containing a minimal GlcNAc tag at the desired Asn or Ser/Thr residue,followed by the enzymatic transfer of preassembled high-mannose,complex or sialylated glycans in a single step from activated oxazoline donors catalyzed by endo-β-N-acetylglucosaminidases(ENGases)like Endo-M,Endo-A or its engineered derivatives.As the glycan attachment is enzymatic,theα/βselectivity and linkage fidelity is identical to that found in nature,as opposed to the epimerization or anomeric mixtures often seen in purely chemical approaches.Recent examples include the preparation of an M6P-decorated cyclic glycopeptide that binds the cation-independent mannose-6-phosphate receptor(CI-MPR)with nanomolar affinity using Endo-A-mediated transfer onto a phosphorylated core followed by in-resin disulfide cyclization.The method is scalable to milligram-to-gram quantities and is also compatible with protecting-group-free carbohydrate donors,making it the approach of choice for the production of reference standards as well as therapeutic candidates.
SPPS-based Glycopeptides
SPPSprovides a fully chemical,modular approach to glycopeptides,in which pre-glycosylated amino-acid building blocks are sequentially coupled directly to the elongating peptide chain on-resin.In the Fmoc(favoured over Boc chemistry as glycosidic bonds are acid-labile)SPPS strategy,the C-terminal residue is first attached to a Rink-amide or Wang resin via a cleavable linker,before C-to-N terminus elongation.During each cycle,the temporary Fmoc group is removed with piperidine,and the next amino acid(standard or glycosylated)activated(HBTU/HOBt)and coupled in excess.O-Glycosylated serine or threonine building blocks are typically protected at the carbohydrate hydroxyls as O-acetyl or O-benzyl groups.N-linked Asn(GlcNAc)derivatives are Fmoc-protected on theα-amine and feature acid-labile side-chain protection.After chain assembly,global deprotection and resin cleavage(TFA/TIS/H2O 95:2.5:2.5)affords the fully deprotected glycopeptide.The approach has been exploited to prepare mucin-type glycopeptides with Tn,TF and STn(tumour-associated)antigens on PDTR epitopes,which have enabled NMR studies to directly relate glycosylation with extended peptide conformations and increased immunogenicity.Limitations to the method include the need for robust protection strategies to suppress epimerization of glycosylated residues and an upper size boundary(~50 residues)set by the inherent limitations of SPPS,though the latter can be circumvented by native chemical ligation of glycopeptide fragments.
Glycopeptides have proven useful at every stage of drug development.For example,synthetic glycopeptide antigens presenting tumor-associated carbohydrate antigens(TACAs)like Tn(GalNAcα-O-Ser/Thr)or sTn(Neu5Acα2-6GalNAcα-O-Ser/Thr)motifs can be designed to overcome B-cell tolerance and drive high-affinity IgG responses when formulated with CpG-oligodeoxynucleotide(CpG-ODN)adjuvants.Site-specific incorporation of unnatural amino acids with azide handles enables click-glycosylation of homogenous glycopeptide immunogens whose glycan density and valency can be rationally controlled to direct germline maturation towards broadly neutralizing antibody lineages.On the other hand,aberrantly core-fucosylated or hypersialylated glycopeptides secreted into the circulation can be used as reliable cancer biomarkers:for instance,the FDA-approved AFP-L3 fraction,a core-fucosylated glycoform ofα-fetoprotein,is predictive of hepatocellular carcinoma with higher specificity than total AFP.ADCs can be designed by enzymatically remodeling the Fc glycan to include aldehyde or azide tags for site-specific conjugation of cytotoxic payloads using hydrazone or strain-promoted azide–alkyne cycloaddition(SPAAC),respectively,affording homogeneous ADCs with pre-determined drug-to-antibody ratios(DAR=2 or 4)and superior therapeutic indices.Injectable glycopeptide hydrogels that co-present ECM-mimetic glycans and integrin-binding peptides offer localized,sustained release of small-molecule drugs or mRNA while also modulating macrophage polarization and oxidative stress to promote tissue repair following myocardial infarction or spinal cord injury.
Multidrug-resistant Gram-positive bacteria are often susceptible to glycopeptide antibiotics,such as vancomycin or teicoplanin.Glycopeptides are natural products with a crosslinked heptapeptide core(connected by aryl–aryl and aryl–ether linkages)with one or two residues of vancosamine or glucosamine.These derivatives increase water solubility and help glycopeptides partition into bacterial membranes.Glycopeptides bind with high affinity(Kd≈10−10 M)to the d-Ala-d-Ala residue at the C terminus of lipid II,a structural analog of peptidoglycan,physically obstructing the transglycosylase and transpeptidase enzymes involved in cell wall cross-linking.Lipoglycopeptides,such as telavancin,are glycopeptide derivatives that have a lipophilic decylaminoethyl side chain.These chains insert into the bacterial membrane and cause rapid depolarization of the membrane potential,which can help kill vancomycin-intermediate S.aureus(VISA)strains.Bacterial strains that overexpressed the vanA or vanB operons,which change the last two residues of peptidoglycan precursors to d-Ala-d-Lac instead of d-Ala-d-Ala,were more resistant to glycopeptides due to decreased binding affinity(3-fold decrease).Glycopeptide hydrogels have been used for local drug delivery and sustained release of antibiotics,and composites loaded with either minocycline or Ag@ZnO nanoparticles were able to eradicate 99%of MRSA biofilms and promote tissue repair in periodontal and chronic wound models.
Glycopeptides are frequently used as reagents in glycomics and proteomics analyses.Isotope–labeled glycopeptide standards(13C6,15N2)with identical chromatographic properties and a known mass difference are added to biological digests for absolute quantification of site-specific glycosylation occupancy by LC-MS/MS.For example,a synthetic[13C6]-Asn42-CTLA-4-Fc glycopeptide with a core-fucosylated biantennary N-glycan is commonly used as an internal standard to measure therapeutic antibody glycosylation during process development.On Q-TOF instruments,precursor ion scanning for the diagnostic oxonium ions(m/z 204.09,HexNAc+;m/z 366.14,HexHexNAc+)released from glycopeptides can be used to initiate data-dependent acquisition for unbiased detection of low-abundance glycoforms.The NIST RM 8761 reference material includes a panel of 27 synthetic glycopeptides with high-mannose,hybrid,and complex glycans,which can be used to harmonize retention-time indices and MS2 spectral libraries across laboratories.Enrichment methods for glycopeptides including hydrophilic interaction liquid chromatography(HILIC),lectin affinity chromatography,or boronate-derivatized monoliths use glycopeptide standards to assess extraction recovery and linear dynamic range for reproducible glycoproteomic quantitation in clinical cohorts.
Fig.1 Schematic diagram of the biological functions of glycopeptide hydrogels.1
Glycopeptides are short peptides that contain one or more covalently attached carbohydrate(glycan)moieties,typically consisting of fewer than 50 amino acids.Glycoproteins,on the other hand,are full-length proteins with glycosylation.Glycopeptides are often used in analytical studies,vaccine development,or as synthetic antigens,while glycoproteins are involved in a broader range of biological processes.
Answer:Yes,we specialize in site-specific glycopeptide synthesis using solid-phase peptide synthesis(SPPS)and chemoenzymatic methods.You can define the exact glycosylation site(e.g.,Asn for N-linked or Ser/Thr for O-linked)and the type of glycan required.We also offer consultation for optimal sequence and glycan design to improve stability and bioactivity.
Absolutely.We provide isotope-labeled glycopeptides,including¹³C,¹⁵N,or deuterium(²H)labeling,for use in mass spectrometry(MS),pharmacokinetic studies,or metabolic tracking.Labeled sites can be placed on either the peptide backbone or the glycan moiety based on your analytical needs.
Every batch undergoes rigorous quality control,including HPLC purity analysis,MS(MALDI-TOF,ESI),and glycan structure validation via NMR or enzymatic digestion when required.We guarantee≥95%purity for research-grade materials,and GMP-level documentation is available for pharmaceutical-grade requests.
Yes,we provide bulk glycopeptide manufacturing ranging from milligram to kilogram scale.For large-scale or GMP-grade production,we offer process optimization,batch records,and regulatory documentation.Whether for preclinical research or commercial applications,we can scale efficiently and cost-effectively.
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