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Small Molecule & Hapten Bioconjugation Services

Custom small molecule and hapten conjugates with full analytical support — from antibodies and proteins to peptides, oligos, and nanoparticles.

Speak to a Scientist Overview Antibody & Protein–Small Molecule
40+ Years of Bioconjugation Experience ISO 9001:2015 / ISO 13485:2016 Custom & OEM / Kit Support Texas, USA
Overview Small Molecules Haptens Antibody & Protein Conjugates Hapten–Carrier Small Molecule–Oligo Solid-Phase Immobilication Lipid & Polymer

peptide conjugation Overview

Small molecule and hapten bioconjugation enables the covalent linkage of drugs, fluorophores, chelators, toxins, enzyme substrates, affinity tags, and immunogenic haptens to antibodies, proteins, peptides, oligonucleotides, nanoparticles, polymers, and surfaces to create targeted therapeutics, immunogens, diagnostics, and imaging agents.

Bio-Synthesis provides high-quality small molecule and hapten bioconjugates — including antibody–drug conjugates, hapten–carrier immunogens, small molecule–protein and peptide conjugates, fluorophore- and chelator-labeled biomolecules, and small molecule–nanoparticle formats — engineered with full analytics and documentation supporting research, preclinical, and diagnostic applications.

Our platform supports a wide range of chemistries including NHS ester, maleimide, carbodiimide (EDC/NHS), click (azide–alkyne, SPAAC, tetrazine–TCO), hydrazide/oxime, and photo- or enzyme-mediated strategies, optimized for controlled loading, minimal aggregation, and robust lot-to-lot reproducibility.

Biomolecule Carrier
Antibody · Protein · Peptide · Oligo · Surface
Conjugation Chemistry
NHS · Maleimide · Click · EDC/NHS · Enzymatic
Small Molecule / Hapten Payload
Drug · Fluorophore · Chelator ·
Hapten
Therapeutic & ADC-Style Conjugates

Antibody–drug conjugates, toxin-labeled antibodies, and receptor-targeted small molecule conjugates for oncology and other indications.

Immunogens, Diagnostics & Imaging

Hapten–carrier immunogens, enzyme labels, chelator–protein conjugates, and fluorophore-labeled biomolecules for ELISA, IHC, flow, and imaging.

Documentation & Scale

Method summaries, CoAs, and optional tech transfer to support preclinical, kit, or OEM programs.

Small molecule and hapten conjugation can be combined with our oligonucleotide bioconjugation and broader bioconjugation services from Bio-Synthesis.

Small Molecule & Hapten Library

The table below summarizes commonly used small molecule classes, example reagents, preferred chemistries, and typical carriers/applications supported by Bio-Synthesis.

Class Representative Examples Common Linker / Chemistry Typical Carriers & Applications
Fluorophores FITC / FAM
TRITC, TAMRA, Rhodamine
Alexa Fluor series (AF488, AF555, AF647)
Cy3, Cy5, Cy7 and related dyes 		Amide coupling via NHS esters (Lys/N-terminus)
Thiol–maleimide addition (Cys)
Click chemistry (azide–alkyne, SPAAC) 		Antibodies, proteins, peptides, oligonucleotides
Flow cytometry, microscopy, in vivo imaging, FRET, probes
Biotin & Affinity Tags Biotin, Desthiobiotin
Biotin-PEGn derivatives 		Amide formation to Lys / N-terminus (NHS)
Thiol–maleimide conjugation
Hydrazone/oxime ligation to carbonyls
Click attachments (e.g., DBCO–azide) 		Antibodies, proteins, peptides, oligos, beads, plates, chips
Capture and pull-down, ELISA, SPR/BLI, enrichment
Metal Chelators / Radiolabels DOTA, DOTATATE, NOTA, DTPA, NODAGA and analogs Amide coupling (NHS / EDC)
Thiol–maleimide
Click chemistry where azide/alkyne versions are used
Metal loading (e.g., Ga, Cu, Lu, Zr) after bioconjugation 		Antibodies, proteins, peptides, nanoparticles
PET/SPECT imaging, radiolabeled tracers, in vivo distribution
ADC-Style Cytotoxic Payloads
(research use)		 Maytansinoids (DM1, DM4)
Auristatins (MMAE, MMAF)
Other linker–payloads supplied with NHS / maleimide 		Lysine-directed NHS ester conjugation
Cysteine-directed maleimide on reduced IgG
Cleavable linkers (Val–Cit, disulfide, hydrazone) or non-cleavable 		Full-length mAbs and fragments
ADC-like constructs for oncology and target validation
Small Molecule Inhibitors & Probes Enzyme inhibitors, receptor ligands
Covalent probes, kinase tool compounds 		Amide formation via EDC/NHS or NHS esters
Thiol–maleimide for Cys labeling
Click chemistry for azide/alkyne-tagged probes 		Proteins, peptides, beads, chips
Affinity probes, target ID, pull-down, mechanism studies
Click Handles & “Invisible” Tags Azide- and alkyne-functional small molecules
DBCO / DIBO / BCN cyclooctynes
TCO and tetrazine reagents 		CuAAC (Cu-catalyzed azide–alkyne)
SPAAC (strain-promoted azide–alkyne)
IEDDA (tetrazine–TCO click) 		Antibodies, proteins, peptides, oligos, surfaces, cells
Bioorthogonal labeling, pre-targeting, modular assembly
Hydrophobic & Lipidic Moieties Cholesterol derivatives
Fatty acids / lipid tails
Bile acid derivatives (e.g., DCA) 		Amide coupling (e.g., to Lys via EDC/NHS)
Click chemistry to oligos or peptides
Formulation-driven assembly into LNPs or micelles 		Oligonucleotides, peptides, polymers, nanoparticles
Delivery, membrane anchoring, formulation interfaces

The table below summarizes typical hapten categories used to generate antibodies or assay antigens, with example structures and preferred use cases.

Hapten Class Representative Examples Common Linker / Chemistry Typical Carriers & Applications
Classic Synthetic Haptens DNP (dinitrophenyl)
TNP (trinitrophenyl)
NP (4-hydroxy-3-nitrophenyl) 		EDC/NHS or NHS esters to Lys on carrier proteins
Isothiocyanate conjugation where applicable
Optional click handles for orientation control 		KLH, BSA, OVA, CRM197
Model immunogens, positive controls, method development
Drug & Metabolite Haptens β-lactam antibiotics (penicillin derivatives)
Small-molecule drugs and metabolites
Selected pesticides / industrial chemicals (where permitted) 		EDC/NHS coupling to carrier lysines
NHS-activated derivatives
Click chemistry when azide/alkyne handles are designed in 		KLH/BSA immunogens, BSA/OVA coating conjugates
Drug monitoring, toxicology, environmental exposure panels
Steroid & Hormone Haptens Estradiol, testosterone, cortisol, progesterone
Thyroid and related endocrine ligands 		Derivatization at non-critical positions to add spacers
EDC/NHS amide formation to carrier proteins 		KLH/BSA/OVA immunogens
Competitive ELISA and other hormone assays
Carbohydrate & Glyco-Haptens Lewis antigens (Lewis A, Lewis X)
Sialyl Lewis X
Tumor-associated carbohydrate antigens (Tn, TF, Globo H, etc.) 		Reductive amination from reducing-end aldehydes
Oxime/hydrazone ligation to carbonyls
Click chemistry when azide/alkyne tags are present 		KLH, BSA or synthetic scaffolds
Anti-glycan antibody generation, oncology and infection markers
Fluorophore & Reporter Haptens Fluorescein, rhodamine derivatives
Other dye haptens for anti-dye antibody generation 		NHS or isothiocyanate coupling to Lys
EDC/NHS where carboxyl groups are available 		KLH/BSA immunogens, ELISA coating antigens
Anti-fluorophore antibodies, labeled standards
Epitope-Mimic Haptens Minimal pharmacophore fragments
Simplified analogs of complex ligands 		EDC/NHS, NHS esters, or click chemistry
Spacer arms to optimize epitope presentation 		KLH/BSA carriers, peptides, synthetic scaffolds
Custom immunogens for epitope-focused antibody campaigns

Antibody & Protein–Small Molecule Conjugates

Antibody and protein–small molecule conjugates combine the specificity of biologics with the potency or functionality of low molecular weight agents. Bio-Synthesis designs and manufactures custom antibody–drug conjugates (research grade), fluorophore- and chelator-labeled antibodies, and protein–small molecule conjugates using optimized chemistries and spacers, delivering controlled loading, low aggregation, and preserved binding.

Antibody / Protein Carrier
mAb · Fab · scFv · Enzyme
Conjugation Chemistry
NHS · Maleimide · Click · Enzymatic
Small Molecule Payload
Drug · Fluorophore · Chelator
Product Highlights
  • Antibody–drug conjugates (research grade) using cleavable and non-cleavable linkers.
  • Fluorophore-labeled antibodies and proteins for flow cytometry, microscopy, and imaging.
  • Antibody & protein–chelator conjugates (e.g., DOTA, NOTA) for radiolabeling.
  • Enzyme–small molecule conjugates for signal amplification and proximity assays.
Preferred Applications
  • Targeted delivery of cytotoxic or modulating small molecules to specific cell types.
  • High-sensitivity detection using fluorophore or enzyme labels.
  • Preclinical screening of ADC linker–payload combinations.
  • Radiolabeled antibody development via metal-chelator conjugates.

Conjugation Strategy
  • Match small molecule handle (amine, thiol, azide, alkyne) to the antibody or protein surface chemistry.
  • Use lysine- or cysteine-directed strategies with control of drug-to-antibody ratio (DAR).
  • Employ PEG or spacer arms to reduce steric hindrance and maintain antigen binding.
  • Monitor DAR and aggregation by intact MS, UV/Vis, and SEC-HPLC.
Formulation & Stability
  • Optimize buffer conditions for both protein and small molecule stability.
  • Include stress testing (temperature, freeze–thaw, agitation) as needed.
  • Confirm binding and activity post-conjugation using relevant functional assays.
  • Define release criteria around DAR, binding, potency, and purity.

Protein / Antibody
Identity, format (mAb, Fab, scFv, enzyme), concentration, and buffer.
Small Molecule
Structure, MW, available handles (amine, thiol, etc.), and stability profile.
Goals
Target DAR or label:protein ratio, preferred chemistry, and functional tests (binding, potency, imaging, etc.).
Specs
Lot size, stability expectations, and documentation required for kit or preclinical use.

Hapten–Carrier Immunogens & Conjugates

Hapten–carrier conjugates link small, non-immunogenic molecules such as drugs, metabolites, steroids, and chemical haptens to immunogenic carrier proteins to elicit high-affinity antibodies. Bio-Synthesis develops custom hapten–KLH, hapten–BSA, hapten–OVA, and other carrier conjugates with tuned loading and defined chemistry to support polyclonal and monoclonal antibody generation.

Carrier Protein
KLH · BSA · OVA · CRM197
Conjugation Chemistry
NHS · EDC/NHS · Maleimide · Click
Hapten Payload
Drug · Metabolite · Steroid · Tag
Product Highlights
  • Drug, metabolite, and pesticide haptens conjugated to KLH/BSA/OVA.
  • Steroid and hormone haptens for endocrine and biomarker panels.
  • DNP, TNP, NP, and other classic haptens for method development and controls.
  • Defined or approximate hapten density with parallel BSA conjugates for ELISA screening.
Preferred Applications
  • Polyclonal and monoclonal antibody production against small molecules.
  • Development of competitive ELISA and other immunoassay formats.
  • Reference immunogens and standards for internal R&D programs.
  • Diagnostic kit and OEM reagent development.

Hapten & Linker Design
  • Position linkers away from critical epitopes on the small molecule where possible.
  • Select appropriate handles (carboxyl, amine, thiol) via hapten derivatization if needed.
  • Use spacer arms to present the hapten away from carrier protein surface.
  • Provide both immunogen (KLH) and coating conjugates (BSA/OVA) when required.
Analytics & Immunization
  • Assess hapten loading by UV, MS, or other appropriate methods.
  • Prepare conjugates in immunization-ready buffers or as lyophilized materials.
  • Coordinate immunization schedules and titer testing as needed.
  • Provide documentation to support assay development and regulatory files.
oligo KLH conjugation
16 mer DNA cojugation to KLH. Denatured PAGE gel analysis demonstrates precise final conjugates vs unconjugated material by Bio-Synthesis.

Hapten
Identity, structure, MW, solubility, and any existing derivatization or handles.
Carrier
Preferred carrier protein (KLH, BSA, OVA, CRM197, or other), concentration, and buffer.
Design Goals
Desired approx. hapten density, immunization species, and assay format (e.g., competitive ELISA).
Assays
Titer and specificity readouts you plan to run, including competitor panel if applicable.

Small Molecule–Oligonucleotide & Aptamer Conjugates

Small molecule–oligonucleotide conjugates integrate the programmability of nucleic acids with the functionality of low molecular weight agents. Bio-Synthesis generates custom oligo–drug, oligo–fluorophore, oligo–chelators, and aptamer–drug conjugates using optimized linkers and chemistries, supporting targeted delivery, biosensing, and imaging applications.

Oligo / Aptamer Scaffold
DNA · RNA · siRNA · Aptamer
Conjugation Chemistry
Click · Amide · Cleavable
Small Molecule Payload
Drug · Fluor · Chelator · Hapten
Product Highlights
  • Aptamer–drug conjugates (ApDCs) for targeted drug delivery and controlled release.
  • Oligo–drug and oligo–metabolite conjugates for mechanistic and delivery studies.
  • Oligo–fluorophore and oligo–quencher constructs for molecular beacons and probes.
  • Oligo–chelators (e.g., DOTA, NOTA) for radiolabeling and imaging applications.
Preferred Applications
  • Targeted delivery and tracking of small molecule payloads via oligo or aptamer recognition.
  • Signal-generating oligonucleotide probes for qPCR, imaging, and biosensors.
  • Radiolabeled oligo constructs for in vivo distribution and binding studies.
  • Oligo-based biosensors and microarray platforms.

Oligo & Aptamer Design
  • Place conjugation sites at termini or regions that avoid disrupting key structural motifs.
  • Use suitable backbones (phosphorothioate, 2′ modifications) where required by biology.
  • Incorporate spacers to distance bulky payloads from hybridization or binding interfaces.
  • Align conjugation strategy with downstream purification and QC methods.
Payload & Linker Considerations
  • Select cleavable linkers (pH-, enzyme-, or redox-sensitive) when controlled release is desired.
  • Use bioorthogonal click chemistry for site-specific modification when possible.
  • Confirm stoichiometry and homogeneity by LC-MS and analytical HPLC/UPLC.
oligo dota conjugation
26 mer DNA conjugate to DOTA with final MW of 8462.65986 Da by Bio-Synthesis.

Oligo / Aptamer
Sequence, chemistry (DNA/RNA/siRNA/aptamer), handles (e.g., 5′-amine, 3′-thiol, azide), and purity.
Small Molecule
Identity, handles (NHS, maleimide, azide/alkyne), and desired linkage type (cleavable vs non-cleavable).
Design Goals
Target stoichiometry, application (delivery, imaging, sensor), and any potency or binding benchmarks.
Assays
Hybridization, binding, uptake, imaging, or functional readouts you plan to use.

Nanoparticle & Surface Small Molecule / Hapten Conjugates

Nanoparticle and surface–small molecule/hapten conjugates enable highly controlled presentation of ligands, haptens, and reporter molecules on gold nanoparticles, magnetic beads, plates, chips, and other solid supports. Bio-Synthesis prepares custom small molecule–NP and hapten–surface reagents with tuned density, blocking, and coating conditions, supporting lateral flow, biosensors, ELISA plates, and microarrays.

Nanoparticle / Surface
Gold NP · Beads · Chips · Plates
Conjugation Chemistry
Thiol–Gold · Biotin–Streptavidin · EDC/NHS
Small Molecule / Hapten
Ligand · Hapten · Reporter
Product Highlights
  • Gold nanoparticle–small molecule and hapten conjugates for lateral flow and plasmonic assays.
  • Magnetic bead–hapten or ligand conjugates for capture, enrichment, and pull-down assays.
  • Plate and chip coatings with ligands, haptens, or small molecule arrays.
  • Custom surface density, blocking strategies, and lot-controlled manufacturing.
Preferred Applications
  • Point-of-care and lateral flow diagnostics using small molecule or hapten labels.
  • Affinity capture and screening with bead-based or chip-based formats.
  • Microarray and biosensor platforms presenting small molecule libraries.
  • High-throughput screening, epitope mapping, or ligand fishing.

Surface Chemistry & Coating
  • Use thiol–gold and biotin–streptavidin chemistries where appropriate for robust attachment.
  • Control ligand density to maintain binding while avoiding steric crowding.
  • Apply PEG or mixed SAM strategies to limit non-specific binding.
QC & Performance
  • Characterize size, polydispersity, and aggregation for nanoparticle conjugates.
  • Evaluate signal-to-background ratio in relevant assay buffers and matrices.
  • Assess batch reproducibility using functional binding or assay performance tests.

Small Molecule / Hapten
Identity, desired density, and any existing handles or linkers.
Nanoparticle / Surface
Gold NP, magnetic bead, plate, chip, or resin type, vendor specs, and size or coating details.
Assay Format
Lateral flow, ELISA, SPR/BLI, microarray, or other assay type, including detection method.
Specifications
Coating density, background thresholds, lot size, and stability targets.

Lipid & Polymer Small Molecule / Hapten Conjugates

Lipid and polymer–small molecule conjugates combine hydrophobic or polymeric carriers with functional payloads to improve delivery, circulation, and formulation compatibility. Bio-Synthesis designs and produces cholesterol-, fatty acid-, PEG-, and polymer–small molecule or hapten conjugates aligned with LNP, micelle, or nanoparticle systems, with supporting analytics and documentation for in vivo and formulation-focused programs.

Lipid / Polymer Carrier
Cholesterol · PEG · PLGA
Conjugation Chemistry
Amide · Click · Hydrophobic Tail
Small Molecule / Hapten Payload
Drug · Ligand · Reporter
Product Highlights
  • Cholesterol- and lipid–small molecule conjugates for improved exposure and uptake.
  • PEGylated small molecules and haptens for solubility and pharmacokinetic tuning.
  • Polymer–small molecule conjugates (e.g., PLGA, dendrimers) for controlled-release systems.
  • Architectures supporting combination with LNP and nanocarrier platforms.
Preferred Applications
  • Systemic delivery of small molecule payloads with tuned PK profiles.
  • Depot and slow-release formulations leveraging polymer–drug conjugates.
  • Targeted liposomal or nanoparticle formulations using small molecule ligands.
  • Bridging between small-scale discovery and scalable formulation platforms.

Lipid / Polymer Design
  • Select lipid or polymer based on target tissue and formulation strategy.
  • Control conjugation position and spacer length to maintain payload bioactivity.
  • Balance hydrophobicity and hydrophilicity to manage solubility and aggregation.
Formulation Interface
  • Align conjugate properties with intended carrier (LNP, micelle, polymer NP, etc.).
  • Characterize physicochemical parameters relevant to your delivery system.
  • Include stability and potency testing in target formulation buffers or vehicles.
cyclic peptide-DOPE lipid conjugation
DOPE-Lipid cyclic peptide conjugation with final MW: 1829.25 by Bio-Synthesis.

Small Molecule / Hapten
Identity, structure, desired loading, and efficacy/stability goals.
Lipid / Polymer
Cholesterol, fatty acid, PEG, PLGA, dendrimer, or other carrier details.
Formulation Plan
Intended carrier system (LNP, micelle, NP, depot) and route of administration.
Specifications
Target potency, release profile, and any constraints from downstream formulation partners.

Technical Summary — Small Molecule & Hapten Bioconjugation Platform

Workflow
  • Project intake and design review (payload, carrier, application, and risk mapping).
  • Conjugation route scouting and linker optimization (cleavable vs non-cleavable, site-selective options).
  • Scale-up with in-process monitoring and process control.
  • Purification and polishing tailored to the conjugate type.
  • QC and documentation aligned with your downstream needs.
Controls & Comparators
  • Unconjugated carrier and payload controls.
  • Variants in linker type, length, conjugation position, and loading level.
  • Cleavable vs non-cleavable conjugate comparisons.
  • Functional benchmarks (binding, potency, assay performance).
Analytics & Documentation
  • Identity and purity by LC-MS, HPLC/UPLC, and SDS-PAGE/SEC as appropriate.
  • Conjugation ratio, aggregation, and functional assays as applicable.
  • Certificates of Analysis and optional tech transfer packages.

FAQ

Which payloads and haptens do you support?

We work with a broad range of small molecules and haptens including drugs, metabolites, pesticides, steroids, dyes, chelators, affinity tags, and classic haptens such as DNP/TNP/NP, provided appropriate safety and handling criteria are met.

Which carriers can you conjugate to?

Carriers include antibodies, proteins, peptides, oligonucleotides, nanoparticles, polymers, and surfaces such as beads, plates, and chips. We can also work with custom carriers under NDA.

Can you both perform derivatization and conjugation?

In many cases, yes. Where small molecules or haptens require derivatization to introduce suitable handles, we can propose and perform derivatization chemistries followed by bioconjugation, purification, and QC.

Do you support diagnostic kit/OEM or regulated projects?

We support projects requiring enhanced documentation, lot control, and stability programs suitable for regulated or kit/OEM environments and can align release criteria with your internal specifications.

What information do you need to scope a small molecule or hapten project?

At minimum, we need the small molecule/hapten structure and MW, carrier identity, intended conjugation type, application, and any required performance metrics (binding, potency, assay readout, or stability).

Can you work under NDA and handle proprietary molecules?

Yes. Bio-Synthesis routinely works under NDA/MSA and treats all structures, materials, and results as confidential.

Contact

Speak to a Small Molecule & Hapten Bioconjugation Scientist

Share your small molecule or hapten, carrier, application, and target performance. We will recommend a conjugation route, linker strategy, and QC package, then provide a project quote.

Request a Quote Feasibility Review OEM / Kit Partner Sample Submission
Email: sales@biosyn.com
Phone: +1-972-420-8505
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Recommended Reading & Bio-Synthesis Resources

  • Hermanson, G. T. (2013). Bioconjugate Techniques, 3rd Ed. Academic Press — Core reference for small molecule–protein, hapten–carrier, and surface bioconjugation chemistries.
  • Chari, R. V. J., Miller, M. L. & Widdison, W. C. (2014). Antibody–drug conjugates: an emerging concept in cancer therapy. Angew. Chem. Int. Ed. — Overview of ADC design and linker–payload strategies.
  • Harlow, E. & Lane, D. (1999). Using Antibodies: A Laboratory Manual. Cold Spring Harbor Laboratory Press — Discussion of hapten–carrier immunogens and assay development.
  • Bio-Synthesis, Inc. — Application notes, technical bulletins, and white papers on custom small molecule, hapten, and biomolecule bioconjugation, available from Bio-Synthesis upon request or via the company website.

Why Choose Bio-Synthesis

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Greetings Researchers,

Please be advised that any information, guidelines, writeups, and oral/video/graphic content on our website are intended solely as general guidelines.
It is the researcher's sole responsibility to conduct thorough research on the designs of the products intended for their experiments before submitting
their designs to Biosynthesis for review of production feasibility.
Thank you for your understanding.

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