HATRIC-LRC

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Do you know the targets of your small molecule?

Dualsystems-Biotech-Switzerland-LRC-TriCEPS-1

HATRIC-LRC for small molecules

Now available at Dualsystems

The TriCEPS technology platform has been further developed by the group of Professor Bernd Wollscheid from the ETH Zürich. The newest LRC platform technology is called HATRIC-LRC (HATRIC Ligand Receptor Capture) and enables to identify the targets of small molecule ligands at the cell membrane of living cells. Further, with the HATRIC platform less cells are needed for an experiment than with the original TriCEPS platform and N-, C-, and O-glycosylated targets can be identified.

The HATRIC-platform technology is based on a trifunctional cross linker called HATRIC. One arm of HATRIC contains an N-hydroxysuccinimid (NHS) to be able to bind to small molecules using a primary amine, the second arm contains a hydrazine to covalently bind the glycans of the unknown target proteins at the cell membrane and the third arm possesses an azide to enrich the target proteins.

In a first step the small molecule containing a primary amine is coupled to HATRIC on its first arm. Then the cells expressing the unknown targets and off-targets are mildly oxidized so that aldehydes form on the glycan moieties of the membrane associated proteins. Now, the second arm of HATRIC coupled to the small molecule is able to bind to the glycans at the cell surface. Once the small molecule binds its target the second arm of HATRIC covalently binds to the glycans of the unknown target proteins. In that state the cells expressing the unknown targets are still alive and the target molecules are in their natural microenvironment at the cell membrane. Due to the covalent link the situation is now fixed and the cells are lysed and the third arm of HATRIC is used to enrich the target proteins. The pulled down proteins are then digested with trypsin and identified and relative quantified by LC-MS/MS. Proteins that are enriched in one treatment arm compared to the other treatment arm are the target candidates.

Link to Samedan Ltd. Pharmaceutical Publishers

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Customers Testimonials – LRC-TriCEPS Service

Testimonials from our customers who have used the LRC-TriCEPS technology – in collaboration with Dualsystems Biotech AG.

University of California San Francisco

"We have been trying to identify a receptor that has been sought after for nearly 30 years by laboratories across the globe. Thanks to Dualsystems service CaptiRec (LRC-TriCEPS), we now have a strong candidate receptor." indexDe'Broski R. Herbert Ph.D.
Assistant Professor in Residence
University of California San Francisco (UCSF)
2015-02-17T14:27:53+00:00
"We have been trying to identify a receptor that has been sought after for nearly 30 years by laboratories across the globe. Thanks to Dualsystems service CaptiRec (LRC-TriCEPS), we now have a strong candidate receptor." De'Broski R. Herbert Ph.D. Assistant Professor in Residence University of California San Francisco (UCSF)

Washington University School of Medicine

"Thanks to LRC-TriCEPS (CaptiRec) technology we were able to identify a long sought receptor of our ligand using genetically-engineered cell lines with the support of Dualsystems".Washington_University_in_StFumihiko Urano, MD, PhD
Samuel E. Schechter Professor of Medicine
Washington University School of Medicine
2015-02-17T14:30:12+00:00
"Thanks to LRC-TriCEPS (CaptiRec) technology we were able to identify a long sought receptor of our ligand using genetically-engineered cell lines with the support of Dualsystems".Fumihiko Urano, MD, PhD Samuel E. Schechter Professor of Medicine Washington University School of Medicine

Centro de Estudos de Doenças Crónicas

New publication in Nature Communications using the LRC-TriCEPS technology in collaboration with Alisson Gontijo
« The fruitful collaboration with Dualsystems Biotech using the LRC-TriCEPS (CaptiRec) technology showed that even on insect cells receptors could be identified »

Cedoc-logoAlisson M. Gontijo,
Principal Investigator at CEDOC
Centro de Estudos de Doenças Crónicas
2015-02-24T07:32:40+00:00
New publication in Nature Communications using the LRC-TriCEPS technology in collaboration with Alisson Gontijo « The fruitful collaboration with Dualsystems Biotech using the LRC-TriCEPS (CaptiRec) technology showed that even on insect cells receptors could be identified » Alisson M. Gontijo, Principal Investigator at CEDOC Centro de Estudos de Doenças Crónicas

Igenica Biotherapeutics

«Leveraging Dualsystems Biotech novel linker technology (LRC-TriCEPS) and its analytical data processing capabilities we were able to identify the heterophilic receptor for a highly-pursued immuno-oncology target.»Igenica-Biotherapeutics-logoDr. Edward van der Horst,
Senior Director, Preclinical Development
Igenica Biotherapeutics
2016-05-09T11:13:08+00:00
«Leveraging Dualsystems Biotech novel linker technology (LRC-TriCEPS) and its analytical data processing capabilities we were able to identify the heterophilic receptor for a highly-pursued immuno-oncology target.»Dr. Edward van der Horst, Senior Director, Preclinical Development Igenica Biotherapeutics

East Tennessee State University

For the ligand sample two unique receptors were identified. Flow cytometry analysis with siRNA induced knockdown of these proteins confirmed that the presence of the protein is needed for CTRP3 binding to occur. CONCLUSION The LRC-TriCEPS methodology was successful in identifying the receptor for CTRP3.Logo East Tennessee State UniversityJonathan M Peterson
Assistant Professor
East Tennessee State University
2016-05-30T15:20:03+00:00
“For the ligand sample two unique receptors were identified. Flow cytometry analysis with siRNA induced knockdown of these proteins confirmed that the presence of the protein is needed for CTRP3 binding to occur. CONCLUSION The LRC-TriCEPS methodology was successful in identifying the receptor for CTRP3.”Jonathan M Peterson Assistant Professor East Tennessee State University

Medizinische Hochschule Hannover

With the support of Dualsystems Biotech and their LRC-TriCEPS technology we were able to identify receptor candidates for our peptide with renoprotective properties in kidney injury.

mh-hannover-logoDr. rer. nat. Inga Sörensen-Zender
Postdoc
Medizinische Hochschule Hannover

 
2016-09-26T10:26:51+00:00
“With the support of Dualsystems Biotech and their LRC-TriCEPS technology we were able to identify receptor candidates for our peptide with renoprotective properties in kidney injury.” Dr. rer. nat. Inga Sörensen-Zender Postdoc Medizinische Hochschule Hannover  

The Rockefeller University

"We are very pleased with the work product of Dualsystems Biotech. The TriCEPS reagent allowed us to identify a novel ligand-extracellular matrix protein receptor interaction, which was not possible using traditional techniques. The Dualsystems team were very helpful in tailoring the experimental conditions to fit our biological question."rockefeller-university-logoManish Ponda, M.D., M.S.
Assistant Professor of Clinical Investigation
The Rockefeller University
2016-10-10T14:21:51+00:00
"We are very pleased with the work product of Dualsystems Biotech. The TriCEPS reagent allowed us to identify a novel ligand-extracellular matrix protein receptor interaction, which was not possible using traditional techniques. The Dualsystems team were very helpful in tailoring the experimental conditions to fit our biological question."Manish Ponda, M.D., M.S. Assistant Professor of Clinical Investigation The Rockefeller University

University of Manitoba

"Every aspect of our experience with Dualsystems Biotech was outstanding.  They provided excellent customer service and technical support throughout the entire process.  Their LRC-TriCEPS technology allowed us to identify several new candidate receptors for our protein of interest in rat primary neurons, and this has created new and exciting avenues for our research."

University of Manitba-logoSari S. Hannila, PhD
Associate Professor, Department of Human Anatomy and Cell Science
Associate Member, Spinal Cord Research Centre
Max Rady College of Medicine, Rady Faculty of Health Sciences
University of Manitoba
2017-06-12T10:05:43+00:00
"Every aspect of our experience with Dualsystems Biotech was outstanding.  They provided excellent customer service and technical support throughout the entire process.  Their LRC-TriCEPS technology allowed us to identify several new candidate receptors for our protein of interest in rat primary neurons, and this has created new and exciting avenues for our research." Sari S. Hannila, PhD Associate Professor, Department of Human Anatomy and Cell Science Associate Member, Spinal Cord Research Centre Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba

Münster University Hospital (UKM)

"Dualsystems Biotech’s approach to receptor identification with the TriCEPS reagent gave us a powerful platform with great support for a successful and fast data generation, when conventional approaches had previously failed."Münster University Hospital (UKM) Dr. rer. nat. Martin Herold
Working group from Prof. Dr. med. Luisa Klotz
Münster University Hospital (UKM), Germany
2017-08-24T14:48:20+00:00
"Dualsystems Biotech’s approach to receptor identification with the TriCEPS reagent gave us a powerful platform with great support for a successful and fast data generation, when conventional approaches had previously failed."Dr. rer. nat. Martin Herold Working group from Prof. Dr. med. Luisa Klotz Münster University Hospital (UKM), Germany

University of Miami, Miller School of Medicine

We are very pleased with the experience and interaction on very high professional level with Dualsystems Biotech. As a result of such collaboration the new receptor MUC5B was identified in human chondrosarcoma cells for the first time for antiproliferative neuropeptide PRP-1. Read more
I would like to thank once again the company and, particularly, Dr Helbling for his attention and collaboration.
Dualsystems-Logo-University of Miami, Miller School of MedicineDr Karina Galoian
Research associate professor
University of Miami, Miller School of Medicine
Department of Orthopedic surgery
Miami, Florida, USA
2017-11-16T08:07:04+00:00
We are very pleased with the experience and interaction on very high professional level with Dualsystems Biotech. As a result of such collaboration the new receptor MUC5B was identified in human chondrosarcoma cells for the first time for antiproliferative neuropeptide PRP-1. Read more I would like to thank once again the company and, particularly, Dr Helbling for his attention and collaboration. Dr Karina Galoian Research associate professor University of Miami, Miller School of Medicine Department of Orthopedic surgery Miami, Florida, USA

QIMR Berghofer Medical Research Institute

“With the help of the team at Dualsystems we confirmed a potential receptor which has lead to a Nature paper submission and successful funding of a research grant. The LRC-TriCEPS experiment was straightforward and the process was cost effective. We look forward to using TriCEPS in the future.”QIMR Berghofer Medical Research Institute LogoAnita Burgess  |  PhD
Hepatic Fibrosis Group
QIMR Berghofer Medical Research Institute, Australia
2017-12-12T13:21:33+00:00
“With the help of the team at Dualsystems we confirmed a potential receptor which has lead to a Nature paper submission and successful funding of a research grant. The LRC-TriCEPS experiment was straightforward and the process was cost effective. We look forward to using TriCEPS in the future.”Anita Burgess  |  PhD Hepatic Fibrosis Group QIMR Berghofer Medical Research Institute, Australia

Biomedical Research Institute

PUBLICATION:  Li Z, Zeppa JJ, Hancock MA, McCormick JK, Doherty TM, Hendy GN, and Madrenas J.  Staphylococcal Superantigens Use LAMA2 as a Coreceptor To Activate T Cells. J Immunol. 2018; 200: 1471-1479.

The identification of a T cell co-receptor for staphylococcal superantigens had been challenging due to the structural features of the interaction and its kinetics.  However, working with Dualstystems Biotech AG, and with Dr. Paul Helbling in particular, and using the LRC-TriCEPS technology, we were able to identify a candidate that was subsequently corroborated by biochemical and functional assays.   We are very happy with this collaboration , and sincerely recommend it for the identification of novel receptor or co-receptor candidates.
(Quim) Madrenas, MD, PhD, FCAHS
Chief Scientific Officer
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, USA
2018-04-19T11:18:18+00:00
PUBLICATION:  Li Z, Zeppa JJ, Hancock MA, McCormick JK, Doherty TM, Hendy GN, and Madrenas J.  Staphylococcal Superantigens Use LAMA2 as a Coreceptor To Activate T Cells. J Immunol. 2018; 200: 1471-1479. The identification of a T cell co-receptor for staphylococcal superantigens had been challenging due to the structural features of the interaction and its kinetics.  However, working with Dualstystems Biotech AG, and with Dr. Paul Helbling in particular, and using the LRC-TriCEPS technology, we were able to identify a candidate that was subsequently corroborated by biochemical and functional assays.   We are very happy with this collaboration , and sincerely recommend it for the identification of novel receptor or co-receptor candidates. (Quim) Madrenas, MD, PhD, FCAHS Chief Scientific Officer Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Torrance, USA

LRC-TriCEPS customers worldwide

Over 200 satisfied customers from 28 countries.

5+

Years working with LRC-TriCEPS

200+

LRC-TriCEPS clients served

50+

Cell types used for LRC-TriCEPS

18+

Years of experience

LRC-TriCEPS publications worldwide

LRC-TriCEPS / HATRIC-LRC Publications

Concerning the LRC-TriCEPS or HATRIC-LRC platforms.

Leukocyte differentiation by histidine-rich glycoprotein/stanniocalcin-2 complex regulates murine glioma growth through modulation of anti-tumor immunity

Francis P RocheIlkka PietiläHiroshi KaitoElisabet O SjöströmNadine SobotzkiOriol NoguerTor Persson SkareMagnus EssandBernd WollscheidMichael Welsh and Lena Claesson-Welsh
Received January 27, 2018, Revision received April 21, 2018, Accepted June 19, 2018, Copyright ©2018, American Association for Cancer Research. PDF

Glycomics and Proteomics Approaches to Investigate Early Adenovirus–Host Cell Interactions

Lisa Lasswitz, Naresh Chandra, Niklas Arnberg, Gisa Gerold jmb Journal of Molecular Biology, doi.org/10.1016/j.jmb.2018.04.039 Received 15 February 2018, Revised 24 April 2018, Accepted 30 April 2018, Available online 7 May 2018.

HATRIC-based identification of receptors for orphan ligands

Nadine Sobotzki, Michael A. Schafroth, Alina Rudnicka, Anika Koetemann, Florian Marty, Sandra Goetze, Yohei Yamauchi, Erick M. Carreira & Bernd Wollscheid Nature Communications, volume 9, Article number: 1519 (2018) doi:10.1038/s41467-018-03936-z Published online: 

Staphylococcal Superantigens Use LAMA2 as a Coreceptor GPCT signaling To Activate T Cells

Zhigang Li, Joseph J. Zeppa, Mark A. Hancock, John K. McCormick, Terence M. Doherty, Geoffrey N. Hendy and Joaquín Madrenas J Immunol January 15, 2018, ji1701212; DOI: https://doi.org/10.4049/jimmunol.1701212  (Published online February 5, 2018) This work was supported by the Canadian Institutes for Health Research. J.M. holds a tier I Canada Research Chair in Human Immunology. The Department of Microbiology and Immunology Flow Cytometry and Cell Sorting Facility and McGill Surface Plasmon Resonance–Mass Spectrometry Facility are supported by the Canada Foundation for Innovation.

Toll like receptors TLR1/2, TLR6 and MUC5B as binding interaction partners with cytostatic proline rich polypeptide 1 in human chondrosarcoma

International Journal of Oncology, published online on: November 9, 2017   doi.org/10.3892/ijo.2017.4199 Authors: Karina Galoian, Silva Abrahamyan, Gor Chailyan, Amir Qureshi, Parthik Patel, Gil Metser, Alexandra Moran, Inesa Sahakyan, Narine Tumasyan, Albert Lee, Tigran Davtyan, Samvel Chailyan and Armen Galoyan Metastatic chondrosarcoma is a bone malignancy not responsive to conventional therapies; new approaches and therapies are urgently needed.

Phenotypic screening—the fast track to novel antibody discovery

ScienceDirekt, doi.org/10.1016/j.ddtec.2017.03.004 Department of Antibody Discovery and Protein Engineering, MedImmune, Milstein Building, Granta Park, Cambridge CB21 6GH, UK Available online 25 April 2017

Identification of Putative Receptors for the Novel Adipokine CTRP3 Using Ligand-Receptor Capture Technology

PLoS One. 2016 Oct 11;11(10):e0164593. doi: 10.1371/journal.pone.0164593. eCollection 2016. Li Y1, Ozment T2, Wright GL1, Peterson JM1,3. We used Ligand-receptor glycocapture technology with TriCEPS™-based ligand-receptor capture (LRC-TriCEPS; Dualsystems Biotech AG). The LRC-TriCEPS experiment with CTRP3-FLAG protein as ligand and>INS as a control ligand was performed on the H4IIE rat hepatoma cell line.

Serum stimulation of CCR7 chemotaxis due to coagulation factor XIIa-dependent production of high-molecular-weight kininogen domain 5

Current Issue – vol. 113 no. 45 – Manish P. Ponda,  E7059–E7068, doi: 10.1073/pnas.1615671113 Contributed by Jan L. Breslow, September 23, 2016 (sent for review August 1, 2016; reviewed by Myron Cybulsky and Carl F. Nathan) Manish P. Pondaa and Jan L. Breslowa,1 Chemokines and their receptors play a critical role in immune function by directing cell-specific movement. C-C chemokine receptor 7 (CCR7) facilitates entry of T cells into lymph nodes. CCR7-dependent chemotaxis requires either of the cognate ligands C-C chemokine ligand 19 (CCL19) or CCL21. Although CCR7-dependent chemotaxis can be augmented through receptor up-regulation or by increased chemokine concentrations, we found that chemotaxis is also markedly enhanced by serum in vitro. To identify potential receptors in an unbiased manner, we used ligand–receptor capture (LRC-TriCEPS) technology as a tool for detecting T-lymphocyte surface proteins that physically interact with H497–K520 (Fig. 5A) (20). Transferrin was used as a control ligand to eliminate nonspecific interactions with the TriCEPS reagent.

Laminin targeting of a peripheral nerve-highlighting peptide enables degenerated nerve visualization

Identification of cell surface receptors for the novel adipokine CTRP3

April 2016, The FASEB Journal, vol. 30 no. 1 Supplement 1249.2 Jonathan M Peterson C1q TNF Related Protein 3 (CTRP3) is a member of a family of secreted proteins that exert a multitude of biological effects throughout the body. Our initial work shows promise in the development of CTRP3-induced cellular processes as a means to combat nonalcoholic fatty liver disease (NAFLD). Clinically, NAFLD is defined as the excessive accumulation of fat in the liver, usually due to obesity, and NAFLD effects 1 in 10 Americans. Our previous data show that when high fat fed mice are treated with CTRP3 they are protected from developing NAFLD. However, the mechanism for this effect remains unclear. The purpose of this project was to identify the unknown receptor that mediates the hepatic actions of CTRP3. .

Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing

Nature Communications 6, Article number: 8732 (2015), doi:10.1038/ncomms9732
Received:
Accepted:
Published online:
Andres Garelli, Fabiana Heredia, Andreia P. Casimiro, Andre Macedo, Catarina Nunes, Marcia Garcez, Angela R. Mantas Dias, Yanel A. Volonte, Thomas Uhlmann, Esther Caparros, Takashi Koyama & Alisson M. Gontijo

A Mass Spectrometric-Derived Cell Surface Protein Atlas

Published: April 20, 2015 – http://dx.doi.org/10.1371/journal.pone.0121314 Cell surface proteins are major targets of biomedical research due to their utility as cellular markers and their extracellular accessibility for pharmacological intervention. However, information about the cell surface protein repertoire (the surfaceome) of individual cells is only sparsely available. Here, we applied the Cell Surface Capture (CSC) technology to 41 human and 31 mouse cell types to generate a mass-spectrometry derived Cell Surface Protein Atlas (CSPA) providing cellular surfaceome snapshots at high resolution. The CSPA is presented in form of an easy-to-navigate interactive database, a downloadable data matrix and with tools for targeted surfaceome rediscovery (http://wlab.ethz.ch/cspa).

Protter

Protter — the open-source tool for visualization of proteoforms and interactive integration of annotated and predicted sequence features together with experimental proteomic evidence. The ability to integrate and visualize experimental proteomic evidence in the context of rich protein feature annotations represents an unmet need of the proteomics community. Protter, a web-based tool that supports interactive protein data analysis and hypothesis generation by visualizing both annotated sequence features and experimental proteomic data in the context of protein topology. Protter supports numerous proteomic file formats and automatically integrates a variety of reference protein annotation sources, which can be readily extended via modular plug-ins. A built-in export function produces publication-quality customized protein illustrations, also for large datasets. Visualizations of surfaceome datasets show the specific utility of Protter both for the integrated visual analysis of membrane proteins and peptide selection for targeted proteomics.

Ligand-based receptor identification on living cells and tissues using TRICEPS

Affiliations ¦ Contributions ¦Corresponding authors Nature Protocols 8, 1321–1336 (2013) doi:10.1038/nprot.2013.072
Published online 13 June 2013

Flex your TRICEPS

Nature Chemical Biology 8, 950 (2012) doi:10.1038/nchembio.1126 Published online 26 November 2012 Identifying ligands for receptors in live cells can provide valuable information, providing insight into signaling pathways as well as drug targets, but these interactions can be difficult to detect and quantify. Frei et al. now report a trifunctional chemoproteomic reagent called TRICEPS that binds glycosylated receptors on live cells and allows for the purification of the ligand-receptor complex and identification of receptor-derived peptides by MS. TRICEPS contains three functional groups: an N-hydroxysuccinimide ester for ligand conjugation, a protein….