Custom Glycosylation of Small Molecules & Nucleic Acids

Precision glycosylation of small molecules and nucleic acids is our area of expertise at Creative Biolabs. We provide custom design and conjugation services that improve solubility, stability, cell targeting, and therapeutic index. Our comprehensive platform supports the whole innovation cycle, from design to delivery, whether you are creating a sugar-modified diagnostic probe, improving RNA pharmacokinetics, or optimizing a glycosylated prodrug.

Why Glycosylate Small Molecules and Nucleic Acids?

In nature, many antibiotics, cardiac glycosides, and natural nucleosides depend on sugar attachments to function. Small molecules and nucleic acids have unique problems compared to proteins and antibodies, including low membrane permeability, immunogenicity, quick clearance, and poor water solubility. Polar carbohydrate moieties can increase RNA/DNA nuclease resistance and increase circulation half-life. With specially designed glycosylation suitable for your study requirements, Creative Biolabs assists in recreating and expanding these well-established advantages.

Custom Glycosylation Strategies

To meet the specific structural and functional needs of your target molecule, Creative Biolabs' custom glycosylation method combines a variety of techniques, including synthetic chemistry, enzyme catalysis, and chemoenzymatic.

Enzymatic Glycosylation

We use highly selective glycosyltransferases and glycosidases to build or modify sugar chains for oligonucleotides and sensitive drug scaffolds. For glyco-modified antisense oligos, RNA therapies, and glycosylated natural product derivatives, this allows for regio- and stereospecific attachment without severe conditions.

Chemical Glycosylation

Our chemical synthesis team can conjugate custom-designed glycosyl donors to small molecules via hydroxyl, amine, or thiol groups, using click chemistry, oxime ligation, or glycosyl halide routes. This strategy is particularly effective when:

• Adding sugar units to hydrophobic anticancer drugs to increase their water solubility
• Developing glycosylated prodrugs that release active payloads during tumor-specific enzyme activity.
• Generating glyco-analogs of approved drugs for patentable IP expansion

Chemoenzymatic Approaches

We use hybrid procedures for difficult situations like multi-site alterations or branching glycans. Initial chemical handles are installed selectively, followed by enzymatic extension of glycan motifs with natural or synthetic sugars. This works particularly well for high-value diagnostic nucleotides, aptamer libraries, and glycoRNAs. Every glycosylation project is customized by us according to the structure, intended use, and functional objective of your molecule. There is no one-size-fits-all. We customize the chemistry to meet your science.

Glycosylated Small Molecules: Smart Chemical Enhancement

Many tiny compounds, including natural chemicals and manufactured pharmaceuticals, get their bioactivity from sugar groups. For receptor binding, solubility, or pharmacokinetics, digitoxin, doxorubicin, and erythromycin all need to be glycosylated. Building on this logic, we assist researchers in:

• Targeting certain tissues through sugar-receptor recognition
• Improving the aqueous solubility of hydrophobic scaffolds
• Developing prodrugs activated by glycosidases in tumors or inflamed tissue
• Creating derivatives of antifungals or antibiotics to increase their spectrum or decrease their toxicity

Both natural and synthetic glycoside variations can be created by our chemists to support your formulation objective or structure–activity relationship (SAR) studies.

Glycosylated Nucleic Acids: Building the Next Generation of Therapeutics

Nucleic acid therapeutics are powerful but vulnerable. Rapid degradation, poor cell penetration, and immune activation often limit clinical success. Sugar conjugation provides a versatile toolbox to address these issues.

We offer:

• Sugar-modified siRNA, miRNA, and antisense oligos with enhanced resistance to nucleases
• Glycosylated aptamers and molecular beacons for higher specificity and prolonged bioactivity
• Customized linker chemistry to attach monosaccharides or complex glycans at the 5' or 3' ends, internal positions, or base modifications
• Nucleotide glycosides that reduce negative charge and improve membrane permeability

GlycoRNA Engineering

An exciting frontier, glycoRNAs are RNA molecules naturally or artificially conjugated with glycans. Recent studies suggest their involvement in immune signaling and receptor modulation. At Creative Biolabs, we synthesize custom glycoRNAs and provide comprehensive glycoRNA analysis services to assess structure, profiling, and biological function. This new molecule type opens doors to RNA-based vaccines, immune modulators, and precision diagnostics.

Analytical Characterization: Choosing the Right Tools for Your Project

Every glycosylation project needs quantitative and structural validation. We match analytical platforms to your research objective:

Not sure which method fits your needs? Contact our experts, we'll help you select the most cost-effective and informative strategy based on your sample type and downstream application.

Talk to an Expert

Our Custom Glycosylation Workflow

At Creative Biolabs, we ensure full transparency and flexibility throughout your project:

1. Sample Submission
   • Your target molecule, required sugar moiety, linkage type, and final application
2. Design Phase
   • Structure and function-based glycosylation strategy
   • Selection of chemical or enzymatic route
   • Modeling potential impact on solubility, stability, or targeting
3. Synthesis & Conjugation
   • In-house synthesis using validated or custom protocols
   • Careful optimization of yield, purity, and stability
4. Analytical Validation
   • Site confirmation, sugar identity, purity assessment
   • Optional in vitro testing of bioactivity or release profiles
5. Final Delivery
   • Fully characterized glycosylated product with COA, method documentation, and usage instructions

Why Choose Creative Biolabs?

✅ Decades of glycoscience expertise

Our team combines synthetic organic chemistry, enzymology, and glycobiology to deliver projects that work in real biological systems.

✅ End-to-end project support

From early design consultation to final product delivery, we provide transparent communication and tailored solutions that align with your research objectives.

✅ Custom, not catalog

Every project is built from scratch based on your target molecule and desired outcome. We never force you into predefined kits or workflows.

✅ Confidentiality and IP protection

We operate under strict confidentiality policies, and all custom products belong exclusively to the client.

Related Services

We support glycosylation across biomolecular classes. Expand your modification strategy with our suite of tailored services:

• Custom Glycosylation of Proteins
  Precision glycoengineering for therapeutic proteins and enzymes.
• Custom Glycosylation of Peptides
  Enhancing immunogenicity, protease resistance, or MHC presentation.
• Custom Glycosylation of Antibodies
  Fc glycan remodeling to modulate ADCC, CDC, and serum half-life.
• Custom Glycosylation of Cell Membranes
  Cell surface engineering for synthetic biology and vaccine delivery.
• Custom Glycosylation of Bacterial Membranes
  Outer membrane glycan tuning for immunomodulation and glyco-display.
• Custom Glycosylation of Lipids
  Synthesis of glycolipids and glycan-functionalized delivery systems.

Creative Biolabs is your reliable partner if you want to use glycosylation to improve the functionality of tiny molecules or nucleic acids. We can help you take your project from idea to reality with everything from chemical synthesis to enzymatic accuracy, from analytical profiling to functional validation. To discuss your objectives and receive a custom quote, get in touch with us.

Reference:

1. Andreu, Alicia, et al. "Enzymatic glycosylation strategies in the production of bioactive compounds." Catalysts 13.10 (2023): 1359. https://doi.org/10.3390/catal13101359

Supports

• GlycoRNA Analysis Technologies
• GlycoRNA-seq: High-Throughput Sequencing of Glycosylated RNAs
• Novel GlycoRNA Imaging: Visualizing GlycoRNAs in Single Cells
• Clier-qPCR: Quantitative Validation of GlycoRNAs