At the core of SEE-CITE lies a clever chemical engineering strategy that overcomes one of photo-crosslinking’s long-standing limitations: inconsistent and messy chemical tags. Traditional photo-crosslinking involves attaching a reactive chemical group to a molecule, which, upon UV light activation, permanently binds to nearby proteins. While this method can reveal where a molecule interacts with a protein, the chemical “footprint” it leaves behind varies substantially between molecules, complicating direct comparisons. SEE-CITE introduces a detachable linker that leaves behind a uniform chemical signature upon crosslinking, enabling highly quantitative and reproducible measurements across different small molecules.

The implications of this uniform tagging system are profound. SEE-CITE effectively converts the qualitative nature of early photo-crosslinking techniques into a powerful quantitative platform. Researchers can now rank how strongly various compounds bind to particular protein sites, assess competitive binding among molecules, and identify previously unobserved off-target interactions. This level of detail is especially critical in drug discovery, where understanding both on-target efficacy and off-target effects can guide safer and more effective therapeutics.

To demonstrate the technology’s promise, the UCLA-led team focused on two FDA-approved kinase inhibitors: dasatinib and ascinimib. Kinases are a key class of enzymes implicated in many cancers, including leukemias, and are major targets for targeted therapies. The study revealed distinct binding patterns that confirmed prior knowledge but also uncovered novel interaction sites. Notably, ascinimib exhibited fewer unintended kinase interactions than dasatinib, which correlates with its improved clinical safety and tolerability profile. This insight underscores SEE-CITE’s potential to differentiate subtle differences in drug-target engagement that can affect patient outcomes.

Beyond validating and extending existing pharmacological data, SEE-CITE’s capabilities make it an indispensable tool for both fundamental biology and clinical drug development. Understanding the exact molecular choreography of small molecules as they engage proteins can illuminate how cellular pathways are modulated in health and disease states. Furthermore, by mapping off-target interactions, scientists can proactively identify and mitigate side effects, a critical step for bringing new drugs safely to market.

The innovation did not stop with the chemistry alone. To handle the complex and rich data generated by SEE-CITE experiments, the researchers enhanced existing bioinformatics software. This upgrade allows for rigorous analysis, efficient data integration, and clearer visualization of binding site landscapes—a crucial element given the vast complexity of proteomic datasets. The seamless interface between chemical innovation and computational analysis represents a holistic approach to tackling molecular interaction challenges.

Historically, drug discovery efforts have been impeded by incomplete knowledge of where and how candidate drugs bind their targets. Techniques like X-ray crystallography and cryo-electron microscopy provide exquisite structural snapshots but are laborious and low throughput. In contrast, photo-crosslinking paired with mass spectrometry offers the ability to probe interactions directly in biological contexts and on a proteome-wide scale. SEE-CITE elevates this method by ensuring that the tagging chemistry is not a bottleneck, but a precise and versatile tool.

The ramifications for diseases beyond cancer are equally exciting. Small molecules modulate a broad swath of biological systems, influencing cholesterol metabolism, liver function, immune responses, and metabolic disorders. SEE-CITE’s capacity to pinpoint binding sites in these diverse contexts promises to accelerate the discovery of novel therapeutics and deepen the understanding of molecular mechanisms underlying complex diseases.

This collaborative research endeavor integrated expertise from UCLA’s renowned departments of biological chemistry and chemical biology, the University of Michigan, leading European institutes, and the global biopharmaceutical firm Daiichi Sankyo. Such multi-institutional cooperation highlights the emerging importance of interdisciplinary approaches in pushing the envelope of bioscience innovation.

Crucially, UCLA has sought to protect this technology through an active patent application, ensuring control over its development and broad accessibility to academic and industry researchers alike. As one of the corresponding investigators, Associate Professor Keriann Backus leads this mission to create tools that comprehensively profile the molecular interactions shaping biology and medicine.

Looking ahead, SEE-CITE may become a standard platform in the chemoproteomic toolkit. Its ability to generate detailed, quantitative binding-site maps fosters a new paradigm where drug candidates can be evaluated holistically, not just for binding affinity but for selectivity and safety profiles at an early stage. As such, the technology aligns perfectly with the growing emphasis on precision medicine and personalized therapeutics.

From elucidating subtle nuances of kinase inhibitors to exploring new frontiers in metabolite-protein interactions, SEE-CITE embodies how chemical biology innovations can propel both scientific understanding and therapeutic advancements. By bridging the gap between molecular chemistry and proteomic biology, UCLA researchers have provided the scientific community a powerful lens to decode the intricate dance of molecules within the living cell.

In essence, the development of SEE-CITE reflects a watershed moment in chemical proteomics—a fusion of chemistry, biology, and computation that elevates the resolution at which we observe and manipulate the fundamental interactions governing life and disease. Its continued application promises to yield discoveries that resonate from the laboratory bench all the way to clinical practice and patient care.

Subject of Research: Small-molecule binding-site discovery, protein–drug interaction mapping, chemoproteomics.

Article Title: Small-molecule binding-site discovery using silyl ether-enabled chemoproteomics

News Publication Date: 27-Apr-2026

Web References:
https://www.nature.com/articles/s41557-026-02127-4

Image Credits: CNSI at UCLA

Keywords

Drug discovery, chemoproteomics, photo-crosslinking, protein binding sites, kinase inhibitors, molecular pharmacology, chemical biology, precision medicine, proteomics, drug safety, small molecules, biochemical methods

Oak Brook, IL – Volume 36 of SLAS Technology includes two editorials, one literature highlight, two original research articles, two reviews and two Special Issue (SI) features.

Editorials

• Mass Spectrometry Applications for High-Throughput Experimentation in Supporting Drug Discovery
  High-throughput experimentation paired with mass spectrometry (MS) is accelerating drug discovery by enabling rapid, parallel analysis of thousands of chemical reactions and biological assays. While challenges such as data management and matrix effects remain, advances in MS technology, direct-to-biology workflows and AI integration are driving end-to-end optimization of the drug discovery process.
• 2^nd EUOS/SLAS Joint Challenge: Prediction of Spectral Properties of Compounds
  The Second Joint Machine Learning Challenge, built on the success of the first EU-OPENSCREEN/SLAS challenge, demonstrates how open, well-curated experimental datasets can accelerate the development of advanced machine learning methods for drug discovery. The editorial outlines the challenge–the full technical descriptions of the winning solutions will be published in SLAS Technology later this year.

Reviews

• Guide to Liquid Volume Measurements: A Review of Methods and Technologies
  This review surveys liquid volume measurement methods and technologies for life science laboratories, covering volumes from picoliters to milliliters across applications in biopharmaceutical and clinical settings. Key attributes evaluated include volume range, precision, accuracy, workflow integration and regulatory compliance.
• Toward Full Automation in Synthetic Biology: A Progressive Conceptual Framework Integrating Robotics and Intelligent Agents
  This article examines the role of robotics and AI in automating synthetic biology workflows, covering progress of physical and cognitive automation in synthetic biology. The authors propose a dual framework for both total automation of the full Design-Build-Test-Learn cycle and progressive automation that can be adapted to diverse laboratory contexts, while addressing the ethical considerations of increasingly autonomous biological research.

Original Research

• Implementation of a Modular Digital Laboratory Infrastructure for SiLA₂ Based Devices
  This article presents a laboratory digitalization framework using open-source software and hardware, demonstrated through a SiLA-based continuous chromatography system for Green Fluorescent Protein (GFP) purification. The framework includes device control, data management, evaluation, and maintenance strategies for software and hardware.
• Low-Cost CNC-Based Media Dispensing System for Biotechnology Laboratories
  A custom Computer Numerical Control-based Automated Media Dispensing System was developed and validated over two years for a plant biotechnology lab, outperforming manual dispensing while maintaining efficiency At approximately one-fiftieth the cost of comparable commercial systems, the modular design offers an accessible and ergonomic automation solution for research laboratories.

Literature Highlight

• Life Sciences and Aging
  This entry in the Life Sciences and Society series by SLAS Technology Associate Editor Kerstin Thurow, PhD, centers on advances in genomics, AI, and senolytic therapies that are giving life sciences increased power to intervene in the aging process, shifting the focus toward extending healthy lifespan rather than longevity alone.

Special Issues

• Robotics in Laboratory Automation
  This editorial introduces the Special Issue (SI) Robotics in Laboratory Automation, which highlights advances in robotic systems that improve experimental precision, reproducibility and throughput. The SI addresses key developments in standardization and intelligent automation while acknowledging current limitations and emerging trends shaping the field.
• Revolutionizing Transcriptomics from Single-Cell Insights to RNA-Based Interventions
  This SI on systems genetics examines gene and molecular interaction networks, utilizing high-throughput sequencing and multi-omics technologies to understand how genetic networks influence phenotypes. It emphasizes the significance of personalized medicine, therapeutic target discovery and biomarker identification through integrated genomic and epigenomic approaches.

All active SLAS Discovery and SLAS Technology call for papers are available at:

This volume of SLAS Technology is available at

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SLAS Technology reveals how scientists adapt technological advancements for life sciences exploration and experimentation in biomedical research and development. The journal emphasizes scientific and technical advances that enable and improve:

• Life sciences research and development
• Drug delivery
• Diagnostics
• Biomedical and molecular imaging
• Personalized and precision medicine

SLAS (Society for Laboratory Automation and Screening) is an international professional society of academic, industry and government life sciences researchers and the developers and providers of laboratory automation technology. The SLAS mission is to bring together researchers in academia, industry and government to advance life sciences discovery and technology via education, knowledge exchange and global community building.

SLAS Technology: Translating Life Sciences Innovation, 2024 Impact Factor 3.7. Editor-in-Chief Edward Kai-Hua Chow, PhD, KYAN Technologies, Los Angeles, CA (USA).

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Journal

SLAS TECHNOLOGY