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.

Immuno-Oncology Discovery from Bristol-Myers Squibb published in Nature

„Vista is an acidic pH selective ligand for PSGL-1“

Identification of a new immune-oncology drug target using the LRC-TriCEPS platform on primary human T-cells.
2019-10-30T12:24:14+00:00
„Vista is an acidic pH selective ligand for PSGL-1“ Identification of a new immune-oncology drug target using the LRC-TriCEPS platform on primary human T-cells.

CuroNZ Ltd



The team from DualSystems Biotech AG has been extremely helpful in delivering scientific advice for CuroNZ’s target identification journey. The quick turnaround time and the precision of NRP2945’s target identification in regard to the utilization of their TRICEPS technology impressed us very much. Meanwhile we could identify another NRP2945 receptor target that was identified by DualSystems as being recruited to the NRP2945-activated membrane receptor complex. An absolute pleasure to work with Paul Helbling’s team.



Frank Sieg, PhD
CSO
CuroNZ Ltd
Mangawhai in New Zealand

2019-07-02T04:49:54+00:00
The team from DualSystems Biotech AG has been extremely helpful in delivering scientific advice for CuroNZ’s target identification journey. The quick turnaround time and the precision of NRP2945’s target identification in regard to the utilization of their TRICEPS technology impressed us very much. Meanwhile we could identify another NRP2945 receptor target that was identified by DualSystems as being recruited to the NRP2945-activated membrane receptor complex. An absolute pleasure to work with Paul Helbling’s team. Frank Sieg, PhD CSO CuroNZ Ltd Mangawhai in New Zealand

University of Oklahoma Health Sciences Center

I was very pleased with my collaboration with the team at Dualsystems. We had to work with difficult cells and the team helped our lab develop modifications to the original protocol to be able to use the TriCEPS approach with our cells. The whole team was very responsive, involved, and knowledgeable and this led to a successful identification of a receptor for our ligand of interest. We have since then confirmed this interaction and we are now getting ready to publish this study, which will have implications in the treatment of ocular injuries.University of Oklahoma Health Sciences Center-Logo

 

Anne Kasus-Jacobi, PhD
Assistant Professor of Research
University of Oklahoma Health Sciences Center
Department of Pharmaceutical Sciences
Oklahoma City, Oklahoma, USA
2018-04-23T11:45:16+00:00
I was very pleased with my collaboration with the team at Dualsystems. We had to work with difficult cells and the team helped our lab develop modifications to the original protocol to be able to use the TriCEPS approach with our cells. The whole team was very responsive, involved, and knowledgeable and this led to a successful identification of a receptor for our ligand of interest. We have since then confirmed this interaction and we are now getting ready to publish this study, which will have implications in the treatment of ocular injuries.   Anne Kasus-Jacobi, PhD Assistant Professor of Research University of Oklahoma Health Sciences Center Department of Pharmaceutical Sciences Oklahoma City, Oklahoma, USA

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

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

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

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 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

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

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  

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

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

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

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

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)

LRC-TriCEPS customers worldwide

Over 200 satisfied customers from 28 countries.

6+

Years working with LRC-TriCEPS

200+

LRC-TriCEPS clients served

50+

Cell types used for LRC-TriCEPS

19+

Years of experience

LRC-TriCEPS publications worldwide

LRC-TriCEPS / HATRIC-LRC Publications

Concerning the LRC-TriCEPS or HATRIC-LRC platforms.

https://www.nature.com/articles/s41586-019-1674-5 Nature volume 574, pages565–570 (2019)
Phage resistance at the cost of virulence: Listeria monocytogenes serovar 4b requires galactosylated teichoic acids for InlBmediated invasion
PLOS Pathogens | https://doi.org/10.1371/journal.ppat.1008032 October 7, 2019
PDF
BMC Research Notes 2018 11:863 https://doi.org/10.1186/s13104-018-3974-5
Laura A. Lopez‑Garcia, Levent Demiray, Sandra Ruch‑Marder, Ann‑Katrin Hopp, Michael O. Hottiger, Paul M. Helbling and Maria P. Pavlou Received: 28 October 2018 – Accepted: 30 November 2018- Published: 5 December 2018 PDF
Maliha Zahid, Kyle S. Feldman, Gabriel Garcia-Borrero, Timothy N. Feinstein, Nicholas Pogodzinski, Xinxiu Xu, Raymond Yurko, Michael Czachowski , Yijen L. Wu, Neale S. Mason and CeciliaW. Lo Biomolecules 2018, 8, 147; doi:10.3390/biom8040147 Received: 24 September 2018 / Accepted: 8 November 2018 / Published: 14 November 2018
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
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.
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: 
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.
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.
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
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.
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.
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. .
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