BOC Sciences, leveraging its robust bioconjugation platform, offers end-to-end ADC development solutions to global research institutions and biopharmaceutical companies, with particularly rich experience and technological advantages in tyrosine conjugation. Our tyrosine conjugation platform overcomes the limitations of traditional lysine and cysteine conjugation methods in terms of site control, drug-loading consistency, and structural homogeneity. It enables the construction of ADCs with higher precision, controllability, and stability, significantly enhancing pharmacokinetic properties and therapeutic index. With highly automated workflows, diverse chemical modification strategies, and flexible customized services, BOC Sciences provides one-stop support from ADC molecular design, conjugation optimization, and analytical characterization to large-scale production.
Lys or Cys conjugation strategies usually involve multiple potential modification sites. In contrast, tyrosine residues are sparsely distributed and mostly surface-exposed in antibody structures. Selective tyrosine modification allows for more controlled site-specific conjugation.
Tyrosine conjugation targets surface tyrosine residues located in non-critical regions of the antibody, preserving its secondary structure and antigen-binding capacity. This enhances functional retention and structural integrity of the ADC.
Given the limited number and predictable distribution of tyrosine residues, site-specific modification allows precise control over the DAR, such as maintaining uniform levels like DAR 2 or 4. This facilitates process scale-up and consistent quality control.
This technique is compatible with various conjugation chemistries, such as diazotization, phenol oxidation, and click chemistry derivatives. It can be used with smart linkers (e.g., pH-sensitive or enzyme-responsive), aiding in the construction of responsive ADC carriers.
Antibodies modified at tyrosine sites can introduce controllable functional handles for subsequent bioorthogonal reactions (e.g., CuAAC, SPAAC), enabling the construction of multifunctional (theranostic) platforms.
BOC Sciences has built a modular ADC construction system targeting tyrosine residues by employing advanced chemical modification strategies and a state-of-the-art conjugation platform. We provide flexible, efficient, and controllable conjugation services. From conjugation site screening and chemistry optimization to high-throughput validation and scale-up production, we offer comprehensive customized support to help clients rapidly advance projects during early drug discovery, structural optimization, and preclinical development, accelerating the market translation of precision therapeutics.
Multiple conjugation strategies are available covering lysine, cysteine, tyrosine, glutamic acid, etc.; a variety of advanced enzymatic conjugation and chemical modification toolkits are in place. The technical team consists of PhDs and process experts with backgrounds in ADC development, ensuring technical depth and delivery efficiency.
Equipped with advanced analytical instruments (UPLC, LC-MS/MS, MALDI-TOF, SEC, IEX, etc.); a complete quality evaluation standard system for ADCs is established to ensure regulatory-compliant data. Multi-dimensional quality control indicators such as antibody modification rate, DAR, free drug content, and antibody aggregation are available.
Full-chain services from candidate screening, small-scale development, pilot scale-up to GMP manufacturing are supported. Flexible cooperation models such as FTE teams, staged delivery, and joint development are available. A rapid response mechanism ensures customer feedback is addressed within 24 hours, and project turnaround cycles are short.
A GMP-grade ADC production platform is established in compliance with international standards; CMC support includes process validation, quality studies, and analytical method transfer. Assistance with IND application documentation, data package preparation, and regulatory consulting is also provided.
The client provides antibody information and the intended payload. The BOC Sciences project team evaluates the antibody structure, screens potential tyrosine conjugation sites, and formulates the project plan.
Small-scale validation is carried out, including comparisons of different conjugation strategies, optimization of reaction conditions, and evaluation of DAR control strategies to quickly achieve proof of concept (POC).
High-purity linker-drugs are synthesized or sourced, followed by conjugation experiments with the antibody to preliminarily evaluate the physicochemical properties of the conjugated products.
Comprehensive analysis is conducted including confirmation of antibody modification sites, DAR determination, stability studies, and drug release assays to generate a complete data package.
Selected ADC candidates undergo pilot-scale verification, including optimization of reaction parameters, scale-up of reactions, and purification process improvement to support subsequent GMP manufacturing.
Detailed technical reports and samples are provided to support the client's clinical application and CMC studies, with ongoing project support and batch reproduction capability.
Tyrosine residues are parts of proteins composed of the amino acid tyrosine (Tyr), characterized by a phenolic hydroxyl (–OH) side chain. As an aromatic amino acid, tyrosine is relatively rare in protein sequences but plays critical roles due to its high chemical reactivity. It participates in redox reactions, can be phosphorylated by specific enzymes, and is commonly used for site-specific modifications. Thus, it is considered a promising conjugation site in antibody-drug conjugates (ADCs).
Tyrosine serves multiple functions in biological systems. Beyond being a protein building block, it plays crucial roles in signal transduction, biosynthesis, and neurological functions. Its phenolic hydroxyl group can be phosphorylated by tyrosine kinases, acting as an important signaling molecule that regulates cell proliferation, differentiation, and immune response. Tyrosine is also the precursor of key bioactive molecules such as dopamine, epinephrine, and thyroid hormones. Due to the predictability of its location in proteins, tyrosine is frequently used as an anchor point for chemical modifications and drug loading in bioconjugation, especially in precision therapies like ADCs.
Tyrosine is classified as a neutral amino acid, though its structure contains a weakly acidic phenolic hydroxyl group with a pKa of approximately 10.1. Under neutral pH conditions, the phenol group usually remains un-ionized, rendering tyrosine neutral in proteins. However, in high pH environments or specific microenvironments, the hydroxyl group may deprotonate, displaying mild acidity. Therefore, tyrosine is generally categorized as a neutral or weakly acidic amino acid, rather than a strongly acidic (e.g., aspartic acid) or basic (e.g., lysine) amino acid.
Tyrosine conjugation is a bioconjugation technique that utilizes the tyrosine residues in antibodies or proteins for site-specific modification. By selectively reacting with the phenolic hydroxyl group of tyrosine, small-molecule drugs, fluorescent labels, polymers, or other functional groups can be stably attached to antibody molecules without disrupting their structure or function. This technique offers advantages such as strong site specificity, controllable conjugation sites, and preservation of antibody activity, making it especially suitable for developing structurally homogeneous and therapeutically stable antibody-drug conjugates (ADCs) and protein-modified products.
Tyrosine conjugation technology finds broad applications in the biopharmaceutical field. Most notably, it is used in constructing antibody-drug conjugates (ADCs), where tyrosine site-specific modification enables uniform and stable drug loading, thereby enhancing therapeutic index and pharmacokinetics. Additionally, tyrosine conjugation is widely used in protein labeling (e.g., fluorescent dyes, radioactive probes), diagnostic reagent development, biosensor construction, and nanomedicine carrier modification. It is particularly valuable in biopharmaceutical development where strict control over conjugation site uniformity and preservation of protein function is required.
