Sulfatase cleavable linkers are a class of chemical linkers specifically cleavable by sulfatase enzymes and are widely applied in precise delivery of antibody-drug conjugates (ADCs), small molecule drugs, and nanocarriers. Through enzyme-mediated drug release mechanisms, these linkers can selectively release active drugs within target tissues or cells, enhancing therapeutic efficacy while minimizing off-target toxicity. BOC Sciences provides comprehensive, customized solutions in the ADC linker field, including linker design, chemical synthesis, purification, and functional validation. With extensive R&D experience and advanced facilities, we offer sulfatase cleavable linkers with high stability, selectivity, and controllable release, supporting multiple drug types and carriers to achieve efficient targeted drug delivery.
Sulfatases are enzymes that participate in the cleavage of sulfate ester bonds in biological systems and play a critical role in regulating many physiological molecules. Sulfatases are involved in various biological processes, including bacterial pathogenesis, cellular signal transduction, and hormone regulation. Moreover, sulfatases are overexpressed in many cancer cells, providing additional selectivity for cancer-targeted ADCs. Sulfatase-cleavable linkers exhibit high stability in human and mouse plasma but are reactive primarily within lysosomes, offering an opportunity for ADCs containing aryl sulfate groups to selectively release payloads at the tumor site.
Fig. 1. Sulfatase cleavable linker in ADCs (BOC Sciences Authorized).
In 2020, Bargh et al. developed a novel ADC using a sulfatase-cleavable linker. This linker displayed high water solubility and stability in human and mouse plasma, while exhibiting high reactivity in lysosomes. In 2021, Bargh et al. further developed an ADC using a new dual-enzyme-cleavable linker, which was susceptible to both aryl sulfatase A and β-galactosidase. They employed a 3-O-sulfo-β-galactose linker, sequentially cleaved by the two enzymes to deliver potent payloads to target cells. The anionic sulfate and pyranose functional groups provided high hydrophilicity, reducing ADC aggregation. Additionally, the 3-O-sulfo-galactose-linked ADC showed pronounced cytotoxicity against HER2-positive SKBR3 cells, comparable to aryl sulfate ADC analogs.
BOC Sciences offers comprehensive and professional support for sulfatase cleavable linker services, covering all stages of drug delivery projects and ensuring clients receive reliable, high-performance linker solutions. By integrating expertise in biochemistry, enzymology, and medicinal chemistry, we provide scientific guidance for the development of ADCs, small molecule drugs, and nanocarriers, helping clients optimize linker structures and drug conjugation strategies. In addition, we offer enzyme sensitivity validation, drug release kinetics analysis, and stability testing to ensure controlled in vivo drug release.
In ADC and targeted drug development, the drug molecule and antibody are core factors determining therapeutic efficacy and safety. BOC Sciences provides professional sulfatase cleavable linker design services, optimizing the linker separately for payloads and antibodies to ensure efficient conjugation, structural stability, and controllable release in target tissues. Our design team integrates expertise in chemistry, enzymology, and drug delivery to provide clients with precise and reliable linker solutions that meet diverse drug delivery needs.
Support conjugation with various carriers including antibodies, small molecules, peptides, and nanoparticles for broad applications. Optimize linker structures to ensure efficient binding and stable release across different carriers, meeting diverse drug delivery needs.
Provide personalized sulfatase cleavable linker design and optimization based on the client's drug type, carrier properties, and delivery strategy. Help improve conjugation efficiency, control release rate, and accelerate R&D progress.
A multidisciplinary team of experts in biochemistry, medicinal chemistry, and molecular design provides support. By combining enzymology, chemical synthesis, and drug delivery system experience, we offer scientific and efficient guidance for linker design and development.
The team has years of experience in ADC and targeted delivery project development, successfully supporting multiple drug and carrier conjugation projects. We have accumulated rich technical and process expertise, effectively addressing challenges during R&D.
Use GMP-compliant production facilities and operational standards to ensure high purity and reproducibility. Strict quality control processes guarantee stable linker performance, providing a reliable foundation for further R&D and preclinical studies.
Offer a complete one-stop service from linker design and chemical synthesis to functional validation and process optimization. Provide technical consultation, experimental data analysis, and optimization recommendations to support smooth project progression to the preclinical stage.
Gain an in-depth understanding of the client's drug molecule type, carrier properties, and target release requirements. Provide feasibility analysis and professional recommendations based on project background to guide subsequent linker design and development.
Conduct customized design based on sulfatase enzymatic characteristics and chemical feasibility. Optimize enzyme-sensitive cores, spacer chain lengths, and spatial structures for efficient conjugation and controllable drug release.
Synthesize high-purity sulfatase cleavable linkers while strictly controlling reaction conditions. Ensure linker stability, structural integrity, and batch-to-batch consistency to meet R&D and preclinical experimental requirements.
Use advanced chromatography, mass spectrometry, and physicochemical analysis techniques to verify linker structure and purity. Evaluate physicochemical properties to ensure product stability and biocompatibility.
Perform enzyme sensitivity testing, drug release kinetics, and carrier conjugation stability analysis. Ensure linkers can be efficiently cleaved during in vivo delivery for precise payload release.
Provide complete technical reports, experimental data, and process documentation. Offer optimization recommendations and follow-up technical support based on project feedback to help clients smoothly advance R&D and preclinical studies.
As glycosidase- and (phospho)esterase-based linkers, sulfatase-cleavable linkers exhibit good hydrophilicity due to their permanently charged sulfate substrates and are primarily expressed in lysosomes. Researchers have rationally designed these linkers to evaluate in vitro cleavage rates before using MMAE as the payload and anti-Her2 antibodies. Compared with classical cleavable Val-Cit and Val-Ala linkers, sulfatase linkers demonstrate comparable cellular potency in Her2+ cell lines. Beyond academic comparisons with standard linkers, sulfatase linkers have recently attracted industrial attention due to their potential for development.
BOC Sciences provides full-process, customized sulfatase cleavable linker services, including linker design, chemical synthesis, purification and analysis, enzyme sensitivity testing, drug release kinetics validation, and stability assessment. We also offer technical consultation, structural optimization, and experimental guidance to help clients optimize drug conjugation strategies at various stages of development. This service meets the R&D needs of ADCs, small molecule drugs, and nanocarriers, providing reliable, controllable, and efficient linker solutions for projects.
Sulfatase cleavable linkers are compatible with a variety of drug carriers, including monoclonal antibodies, small molecule drugs, proteins, and nanoparticles. By optimizing the linker structure, efficient conjugation and stable binding with different carriers and drug molecules can be achieved, while ensuring controllable release within target tissues or cells. This broad compatibility makes sulfatase cleavable linkers an ideal choice for ADC development, protein drug modification, and nanomedicine delivery, meeting the needs of diverse drug systems.
To ensure in vivo stability, sulfatase cleavable linkers are typically optimized chemically and structurally, including spacer chain design, so that they remain stable in blood and bodily fluids and resist nonspecific degradation. Drug release primarily relies on specific enzymatic cleavage by sulfatases within target tissues or cells, achieving precise and controllable release. This strategy maximizes therapeutic efficacy, minimizes side effects, and supports the development of various drug delivery systems.
Yes, BOC Sciences' sulfatase cleavable linker service strictly follows GMP standards. We provide high-quality, reproducible linker products to ensure reliability for experiments and preclinical studies. Full-process quality control, including synthesis, purification, functional validation, and technical documentation, supports smooth project progression during early R&D and preclinical stages, ensuring safety and scientific integrity.
Yes. By optimizing the enzyme-sensitive core, spacer chain length, and linker spatial configuration, BOC Sciences can achieve rapid release, sustained release, or controlled release profiles. This adjustability can be customized for different drugs and targeting requirements, ensuring efficient payload release in target tissues while minimizing off-target exposure. This functionality provides flexible design options for ADCs, small molecule drugs, and nanocarriers, supporting diverse therapeutic strategies.
Background
A pharmaceutical company in Germany was developing an ADC for treating advanced breast cancer, with DM1 (a maytansinoid derivative) as the payload and a HER2-targeting monoclonal antibody. The research team aimed to achieve controllable intracellular drug release using a sulfatase cleavable linker to enhance efficacy and reduce off-target toxicity. Traditional nonspecific linkers lacked sufficient in vivo stability, leading to premature drug release, reduced efficacy, and increased side effect risk.
How BOC Sciences Helped?
BOC Sciences provided a comprehensive sulfatase cleavable linker solution. First, we evaluated the structures of the DM1 payload and HER2 antibody, as well as the conjugation sites, and proposed an optimized enzyme-sensitive core design. Then, we customized a high-purity linker according to client requirements, performed chemical modifications and spatial structure optimization, ensuring in vivo stability and enzyme specificity. Functional validation, including sulfatase sensitivity testing and drug release kinetics analysis, was conducted to guarantee efficient drug release in the tumor environment.
Implementation Process
Key Results
With support from BOC Sciences, global clients have utilized our products and custom services to conduct research, resulting in multiple high-quality scientific publications.
"We were developing a new ADC targeting HER2 and required a reliable sulfatase cleavable linker with high stability and precise enzyme sensitivity. BOC Sciences provided customized design and synthesis, enabling our project to progress smoothly."
— Dr. James Walker, Senior Scientist (UK)
"Facing tight timelines for preclinical ADC studies, we needed high-purity sulfatase cleavable linkers with robust functional validation. BOC Sciences delivered exceptional results with detailed technical support, exceeding our expectations."
— Dr. Emily Carter, R&D Manager (USA)
"Our team required a sulfatase cleavable linker compatible with both small molecule payloads and antibodies. BOC Sciences offered tailored solutions, accurate characterization, and timely delivery. Their expertise greatly accelerated our ADC development."
— Dr. Lucas Müller, Principal Investigator (Germany)
"We sought a partner to optimize sulfatase cleavable linkers for in vivo targeted drug delivery. BOC Sciences provided high-quality synthesis, enzyme sensitivity testing, and practical advice, ensuring reliable performance in our studies."
— Dr. Claire Dupont, Senior Research Scientist (France)
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