Custom Protein-Small Molecule Conjugation Service
Are you facing challenges in developing highly specific antibodies, long therapeutic development cycles, or difficulty creating sensitive immunoassay reagents? Our Custom Protein-Small Molecule Conjugation Service helps you accelerate your research and therapeutic development by creating precisely engineered biologics. Through advanced bioconjugation chemistry, state-of-the-art protein engineering, and comprehensive analytical characterization, we deliver functional conjugates tailored to your exact specifications, transforming your scientific concepts into tangible results.
Introduction to Protein-Small Molecule Conjugation
The covalent linkage of a small molecule to a protein or antibody is a cornerstone of modern biotechnology, enabling the creation of hybrid molecules with novel functions that neither component possesses alone. This powerful technique addresses a fundamental challenge in biology: many small molecules, such as haptens, therapeutic payloads, or reporter tags, are either non-immunogenic or cannot target specific cell populations. By conjugating them to a larger, functional protein, their capabilities are dramatically enhanced.
Scientific literature validates this approach as a transformative tool in medicine. The development of Antibody-Drug Conjugates (ADCs) represents a landmark achievement, where highly potent cytotoxic small molecules are linked to monoclonal antibodies that specifically target tumor-associated antigens. This strategy creates a "guided missile" that delivers a therapeutic payload directly to cancer cells, significantly widening the therapeutic window and minimizing off-target toxicity. This principle has led to several FDA-approved therapies that have changed the standard of care in oncology. The core of this success lies in precise chemical control over the conjugation process, ensuring the stability, specificity, and potency of the final construct.
Fig. 1 Structural elucidation of ADCs using the IgG crystal structure.1
Advantages of Protein-Small Molecule Conjugates
- Enhanced Immunogenicity
- Targeted Delivery
- Improved Pharmacokinetics
- Enabling Versatile Research Tools
Key Applications
Antibody-Drug Conjugate (ADC) Development: The design and synthesis of ADCs for targeted cancer therapy is a primary application, combining the tumor-targeting ability of an antibody with the cell-killing power of a cytotoxic small molecule.
Custom Antibody Production: Generating polyclonal and monoclonal antibodies against non-immunogenic small molecules, such as drugs, metabolites, or environmental toxins, for research and diagnostic purposes.
Immunoassay Development: Creating critical reagents for ELISA, lateral flow assays, and other immunodiagnostic platforms by conjugating haptens to carrier proteins for use as immunogens or coating antigens.
Cellular Imaging and Analysis: Labeling antibodies and proteins with fluorescent dyes, enzymes, or biotin to create probes for use in immunohistochemistry (IHC), immunofluorescence (IF), flow cytometry, and Western blotting.
Discover How We Can Help
At Creative Biolabs, we translate the complexity of bioconjugation chemistry into a streamlined, reliable service that delivers functional, well-characterized conjugates to advance your research. We partner with you to understand your project goals and design a conjugation strategy that meets your specific needs, from early-stage discovery to preclinical development. Our service provides you with a direct path to obtaining the critical reagents required for your next breakthrough, whether it's a novel therapeutic candidate, a sensitive diagnostic assay, or a powerful research tool.
Types of our Custom Protein-Small Molecule Conjugation Service
Our service is a fully integrated solution that can be tailored to your specific entry point, whether you have all components ready or require support from the ground up.
Small Molecule Synthesis and Modification
We can synthesize novel small molecules or modify existing ones to incorporate specific functional groups (e.g., amine, carboxyl, thiol, azide) required for conjugation. We handle a wide range of molecules, including cytotoxic payloads, fluorescent dyes, biotin derivatives, and custom haptens.
Recombinant Protein & Antibody Expression
Our team can produce high-purity recombinant proteins and monoclonal antibodies in various expression systems (mammalian, bacterial, yeast) to serve as the carrier for your small molecule.
Linker Design and Synthesis
We provide expertise in selecting and synthesizing a wide array of linkers （both cleavable and non-cleavable) to ensure the optimal stability and release profile for your application.
Conjugate Characterization and Analysis
Every conjugate we produce undergoes rigorous analytical testing, including mass spectrometry to confirm conjugation, HPLC to assay purity, and the drug-to-antibody ratio (DAR).
Our Integrated Workflow
Our workflow is a systematic, phase-gated process designed for transparency and quality, ensuring your project progresses efficiently from concept to delivery.
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Required Starting Materials:
- The chemical structure, purity, and quantity of the small molecule, along with information on its reactive functional groups.
- For the protein/antibody, its concentration, buffer composition, and purity data. If production is required, the gene sequence will be needed.
- A clear outline of the project goals, including the intended application of the final conjugate and any specific performance requirements.
- Key Steps Involved:
| Step | Description | Outcome |
|---|---|---|
| Consultation & Strategic Design | We begin with an in-depth consultation to understand your objectives. Our experts will propose a detailed conjugation strategy, including the choice of chemistry, linker technology, and analytical plan. | A comprehensive project plan with defined milestones and deliverables. |
| Reagent Preparation & Qualification | This stage involves the synthesis or procurement of the small molecule and linker, and the expression and purification of the protein or antibody. All starting materials undergo strict quality control. | Qualified, conjugation-ready small molecules and proteins. |
| Conjugation Reaction & Optimization | Our scientists perform small-scale test conjugations to optimize reaction conditions (e.g., molar ratios, pH, temperature) to achieve the desired level of conjugation. | An optimized protocol for consistent and efficient conjugation. |
| Scale-Up and Purification | Using the optimized protocol, the conjugation reaction is performed at the desired scale. The resulting conjugate is then meticulously purified using advanced chromatography techniques (e.g., SEC, HIC, IEX) to remove unreacted components. | A highly purified protein-small molecule conjugate. |
| Comprehensive Analytical Characterization | The final conjugate undergoes a full panel of analytical tests to confirm its identity, purity, concentration, and key attributes like the drug-to-antibody ratio (DAR). | A fully characterized conjugate that meets all pre-defined specifications. |
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Final Deliverables:
- The purified, ready-to-use protein-small molecule conjugate at the agreed-upon quantity.
- A comprehensive Certificate of Analysis (CoA) detailing the results from all analytical tests, including mass spectrometry, HPLC analysis, and concentration measurement.
- Estimated Timeframe: The typical timeframe for a standard conjugation project ranges from 4 to 8 weeks. This can vary depending on the complexity of the project, such as the need for de novo protein expression or multi-step small molecule synthesis.
Why Choose Us?
Choosing Creative Biolabs means partnering with a team of dedicated scientists committed to the success of your project. Our key advantages include:
- Deep Scientific Expertise: Our team combines extensive experience in both protein chemistry and complex organic synthesis, ensuring your project is managed with scientific rigor from start to finish.
- Client-Centric Partnership: We work as an extension of your team, providing a consultative, transparent, and responsive service tailored to your unique project goals.
- Uncompromising Quality and Reliability: Leveraging state-of-the-art facilities and rigorous quality control systems, we deliver conjugates that are reliable, reproducible, and ready for your critical applications.
- Proven Track Record: We have a history of successfully developing complex conjugates for a diverse range of clients, from academic research institutions to leading biopharmaceutical companies.
Customer Reviews
"Using Creative Biolabs' Custom Protein-Small Molecule Conjugation Service in our research has significantly facilitated our ADC development program. They successfully conjugated our novel cytotoxic payload to our antibody with excellent control over the drug-to-antibody ratio (DAR), providing us with a highly homogeneous conjugate that showed consistent performance in our in vivo studies."
— Dr. Elara Vance [June 2025]
"We were at a standstill trying to develop an antibody for a challenging small molecule metabolite. Creative Biolabs' team not only synthesized the hapten but also expertly conjugated it to KLH. The resulting immunogen was a game-changer, allowing us to generate a high-affinity polyclonal antibody."
— Dr. Samuel Chen [March 2025]
"Outsourcing our protein biotinylation to Creative Biolabs was one of the best decisions we've made. The quality of the biotinylated protein we received was far superior to our in-house attempts. It's a reliable reagent that has saved my team countless hours of troubleshooting."
— Dr. Marco Rodriguez [January 2025]
FAQs
What types of functional groups on my protein and small molecule can be used for conjugation?
A: We can target a variety of functional groups. For proteins, the most common targets are the primary amines on lysine residues and the sulfhydryl groups on cysteine residues. For small molecules, we typically work with active esters, carboxyls, amines, thiols, and click-chemistry handles like azides or alkynes. We will consult with you to determine the best strategy based on your specific molecules.
What carrier proteins do you recommend for generating an immune response to a small molecule?
A: For generating a robust immune response, Keyhole Limpet Hemocyanin (KLH) is generally the most effective and widely used carrier protein due to its large size and high immunogenicity. Bovine Serum Albumin (BSA) is another excellent, cost-effective option commonly used for screening and assay development.
Can you manage the entire process, including producing my antibody and synthesizing the small molecule?
A: Yes. Our service is designed to be a complete solution. We can start with just the sequence of your antibody and the structure of your small molecule. Our integrated workflow includes recombinant antibody production, small molecule synthesis, and the final conjugation and characterization, providing a seamless experience from start to finish.
What level of purity can I expect for my final conjugate?
A: We consistently deliver conjugates with high purity, typically >95% as determined by SDS-PAGE and Size Exclusion Chromatography (SEC-HPLC). Our multi-step purification process is designed to effectively remove any unreacted antibody, free small molecule, and aggregates, ensuring you receive a product of the highest quality for your experiments.
How to Contact Us?
At Creative Biolabs, we are dedicated to providing the scientific expertise and technical capabilities you need to succeed. Our Custom Protein-Small Molecule Conjugation Service is more than a transaction; it's a collaborative partnership aimed at accelerating your path to discovery. Contact us to learn more details.
Reference
- Feng, Yang et al. "Conjugates of Small Molecule Drugs with Antibodies and Other Proteins." Biomedicines vol. 2,1 1-13. 24 Jan. 2014, doi:10.3390/biomedicines2010001. Under an open access license CC BY 3.0, without modification.