Glycopeptides Synthesis Service
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On the basis of extensive experience in peptide synthesis, Creative Peptides proudly offers the most comprehensive glycopeptides synthesis services to our worldwide clients. Our scientists are committed to deliver high quality glycopeptides which will go through strict mass spectral and HPLC analysis to meet our customers' demands.
In recent years, more and more attention has been focused on the function of glycopeptides in immunology realm. It is well-known that a majority of key molecules, which are involved in innate and adaptive immune response, and some secondary metabolites produced by microorganisms are all glycopeptides. And the glycosylation of immunoglobulins plays key role in the regulation of immune reactions: glycans located at various sites modulate a diversity of immunoglobulin properties, including protein conformation, stability, serum half-life and binding affinity. In the meantime, changes in glycans or glycopeptides may also be involved in a variety of human immune-related diseases, such as rheumatoid, autoimmune disease, Wiskott-Aldrich syndrome, infection disease and even cancer. In this way, synthetic glycopeptides have provided a unique frontier for the investigation and better understanding in both glycobiology and proteomics and also contribute to the development of either biotechnological or therapeutic applications.
What is Glycopeptide?
Glycopeptides are a diverse and intricate class of biomolecules that play crucial roles in various biological processes. Comprising a peptide backbone adorned with complex carbohydrate moieties, glycopeptides exhibit remarkable structural diversity, contributing to their functional versatility. The term "glycopeptide" refers to the combined structure of the peptide/protein and the attached glycans.
What is The Function of Glycopeptides?
Targeting Gram-Positive Bacteria: Glycopeptides are primarily used to target and eliminate Gram-positive bacteria, which are characterized by their thick peptidoglycan cell wall. This class of antibiotics is particularly effective against a variety of pathogenic Gram-positive organisms, including Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis. Their ability to specifically target and disrupt the cell wall of these bacteria makes them crucial in treating infections where other antibiotics may be ineffective.
Combating Antibiotic Resistance: One of the most significant functions of glycopeptides is their role in managing bacterial infections resistant to other antibiotics. They are essential in treating strains that have developed resistance to commonly used antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). This ability to address resistant strains underscores the importance of glycopeptides in maintaining effective treatment options for difficult-to-treat infections.
Treating Severe Infections: Glycopeptides are often reserved for severe and life-threatening infections due to their potent antibacterial properties. They are employed in the treatment of serious conditions such as endocarditis (infection of the heart valves), osteomyelitis (bone infections), and complicated skin and soft tissue infections. Their effectiveness in these critical situations highlights their importance in managing severe bacterial infections where other therapies might not suffice.
Supporting Antibiotic Stewardship: By providing an effective treatment option for resistant and severe infections, glycopeptides support broader antibiotic stewardship efforts. Their use helps to preserve the effectiveness of other antibiotics by providing targeted treatment alternatives when first-line therapies fail. This function is vital in controlling the spread of antibiotic-resistant bacteria and ensuring the continued efficacy of existing antibiotics.
How do glycopeptides work?
Glycopeptides work primarily by targeting and disrupting bacterial cell wall synthesis, which is essential for the structural integrity and survival of Gram-positive bacteria. Here's a detailed explanation of their mechanism of action:
Binding to Peptidoglycan Precursors: Glycopeptides specifically bind to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of peptidoglycan precursors in the bacterial cell wall. Peptidoglycan is a key component of the Gram-positive bacterial cell wall, composed of long chains of sugars and amino acids that are cross-linked to form a rigid structure.
Inhibition of Cell Wall Cross-Linking: By binding to the D-Ala-D-Ala residues, glycopeptides prevent the proper cross-linking of peptidoglycan chains. This cross-linking is catalyzed by the enzyme transpeptidase, which is crucial for strengthening the cell wall and maintaining its structural integrity.
Disruption of Cell Wall Integrity: The inhibition of cross-linking leads to a weakened cell wall. The bacterial cell wall becomes less rigid and more permeable, making it unable to withstand the internal osmotic pressure. This increased permeability contributes to cell lysis (bursting) and death due to osmotic pressure imbalances.
Bactericidal Effect: The primary effect of glycopeptides is bactericidal, meaning they kill bacteria rather than merely inhibiting their growth. The destruction of the bacterial cell wall and subsequent cell lysis result in the elimination of the pathogen from the infected site.
Specificity to Gram-Positive Bacteria: Glycopeptides are particularly effective against Gram-positive bacteria because of the unique structure of their cell walls, which contains a thicker peptidoglycan layer compared to Gram-negative bacteria. The specificity of glycopeptides for the D-Ala-D-Ala motif and their inability to penetrate the outer membrane of Gram-negative bacteria limits their effectiveness against these organisms.
Classification of Glycopeptides
Glycopeptides are a unique class of antibiotics and biomolecules characterized by their peptide backbone coupled with carbohydrate (glycan) moieties. This glycosylation can occur at different sites and involves various linkage types, affecting the structure, function, and biological roles of the glycopeptides. Their ability to bind specifically to bacterial cell walls or other biomolecules makes them crucial in both therapeutic and biological contexts. Understanding the different types of glycopeptides, based on their glycan attachment and location within the peptide chain, provides insights into their diverse functions and applications.
Classification Based on Glycan Attachment Type
N-Linked Glycopeptides: N-linked glycopeptides are distinguished by glycans attached to the nitrogen atom of asparagine residues in the peptide chain. This type of glycosylation is the most prevalent, occurring via an N-glycosidic bond in the Asn-X-Ser/Thr consensus sequence. The attachment of glycans at asparagine residues influences protein folding, stability, and interactions, making N-linked glycopeptides critical in a variety of biological processes and therapeutic applications. Examples include many glycoproteins such as erythropoietin and antibodies.
O-Linked Glycopeptides: O-linked glycopeptides feature glycans attached to the hydroxyl groups of serine or threonine residues, and occasionally to lysine, proline, or tyrosine. This type of glycosylation involves an O-glycosidic bond without a specific consensus sequence, allowing for diverse attachment sites. O-linked glycosylation is essential for protein functions like mucin production and cellular adhesion. It affects protein stability and interactions, contributing to the biological roles of mucin-type glycoproteins and other cellular proteins.
C-Linked Glycopeptides: C-linked glycopeptides are characterized by glycans attached directly to the carbon atom of tryptophan residues. This less common glycosylation involves a C-glycosidic bond and is observed in specific contexts such as certain bacterial and fungal proteins. The rarity of C-linked glycopeptides and their unique bonding provide specialized functions and structural properties, although they are less well-understood compared to N- and O-linked types.
Classification Based on Glycan Attachment Site
N-Terminal Glycopeptides: N-terminal glycopeptides have glycans attached at the N-terminus of the peptide chain, either directly to the first amino acid or a modified N-terminal residue. This type of glycosylation can influence the peptide's stability and biological activity. N-terminal modifications are less common but can be critical for specific peptide functions, such as receptor binding and signal transduction, seen in some glycosylated hormones and peptides.
Internal Glycopeptides: Internal glycopeptides feature glycan attachments within the peptide sequence, typically at asparagine, serine, or threonine residues. This internal glycosylation plays a crucial role in protein folding, stability, and functionality. Observed in many glycoproteins like antibodies and membrane proteins, internal glycosylation affects interactions with other cellular components and is vital for proper protein function and immune responses.
C-Terminal Glycopeptides: C-terminal glycopeptides have glycans attached at the C-terminus of the peptide chain. The glycan attachment at the end of the peptide can influence its stability and interactions with other molecules. Although less frequent, C-terminal glycosylation can impact peptide functions in signaling and cellular recognition, contributing to the regulation of protein activity and interactions in various biological contexts.
Advantages of Glycopeptides
Effectiveness Against Resistant Strains: Glycopeptides are particularly valuable in treating infections caused by Gram-positive bacteria that are resistant to other antibiotics. This includes challenging pathogens like methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The unique mechanism of glycopeptides, which involves binding to the D-alanyl-D-alanine terminus of bacterial cell wall precursors, makes them effective even against strains that have developed resistance to other antibiotic classes. Their ability to target and disrupt the cell wall synthesis of these resistant bacteria provides a critical option for managing severe and complicated infections.
Broad Spectrum: Glycopeptides possess a broad spectrum of activity against Gram-positive bacteria, including many that are difficult to treat with other antibiotics. They are effective against a range of pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis. This broad spectrum makes glycopeptides versatile tools in the treatment of various infections, including skin and soft tissue infections, bone and joint infections, and endocarditis. Their broad coverage ensures that they can be used in a variety of clinical situations, especially when other treatment options are limited.
Low Resistance Development: One of the key advantages of glycopeptides is their relatively low rate of resistance development compared to other antibiotic classes. The specific and unique binding mechanism of glycopeptides to bacterial cell wall precursors means that bacteria have fewer mechanisms to counteract their effects. This lower resistance rate is beneficial for maintaining the effectiveness of these antibiotics over time, although vigilance and prudent use are still necessary to prevent the emergence of resistant strains. This characteristic ensures that glycopeptides remain a reliable option in the antibiotic arsenal.
Effective in Serious Infections: Glycopeptides are often reserved for treating serious and life-threatening infections due to their potent activity and efficacy. They are particularly effective in cases where other antibiotics may be inadequate, such as in the treatment of endocarditis (infection of the heart valves), osteomyelitis (bone infection), and complicated skin and soft tissue infections. Their strong antibacterial action and ability to target severe infections make them a crucial component in managing complex clinical scenarios where other treatments may not be effective.
Applications of Glycopeptides in Biology and Medicine
Cellular Recognition and Signaling: Glycopeptides play a crucial role in cell recognition and signaling processes. The glycan structures on cell surface glycoproteins act as recognition motifs, facilitating interactions with other cells or extracellular molecules. These interactions are involved in critical biological processes such as immune response, cell adhesion, migration, and tissue organization.
Immunology and Vaccines: Glycopeptides are key components in the development of glycopeptide-based vaccines. By incorporating pathogen-specific glycan antigens, vaccines can induce a targeted immune response. Glycopeptide-based vaccines have shown promise in generating protective antibodies against pathogens and can potentially be used for the prevention and treatment of infectious diseases.
Antibiotics: Antibiotic glycopeptides, such as vancomycin and teicoplanin, are widely used in clinical settings to combat bacterial infections. These glycopeptides inhibit bacterial cell wall synthesis by binding to specific targets, making them effective against Gram-positive bacteria. However, the emergence of antibiotic resistance poses a challenge, necessitating the development of new glycopeptide antibiotics or alternative approaches.
Biomarkers and Diagnostics: Glycopeptides and their associated glycans can serve as biomarkers for various diseases, including cancer and genetic disorders. Alterations in glycosylation patterns are often associated with disease states, making glycopeptides valuable diagnostic markers. Detection and analysis of glycopeptide biomarkers can provide insights into disease progression, aid in early detection, and guide personalized medicine approaches.
Our Glycopeptides Synthesis Services
- N-Linked Glycopeptides Synthesis
- O-Linked Glycopeptides Synthesis
- C-Linked Glycopeptides Synthesis
- Glycopeptide-based Vaccine Development
- Glycopeptide Antibiotic Development
- Customized Glycopeptides Design
Glycoamino acids we can provide
References
- Pace J L, Yang G. Glycopeptides: update on an old successful antibiotic class[J]. Biochemical pharmacology, 2006, 71(7): 968-980.
- Buskas T, Ingale S, Boons G J. Glycopeptides as versatile tools for glycobiology[J]. Glycobiology, 2006, 16(8): 113R-136R.
