HATRIC-LRC for small molecules
Now available at Dualsystems
The group of Professor Bernd Wollscheid from ETH Zurich showed in their latest publication that HATRIC-LRC (HATRIC Ligand Receptor Capture) enables the identification of the targets of a small molecule at the cell membrane of living cells to elucidate the mode of action of the molecule. Further, it was demonstrated that the HATRIC-LRC technology platform needs less cells for target identification than the previously published LRC-TriCEPS method and it enables the identification of N-, C-, and O- glycosylated targets.
Target identification using HATRIC-LRC is based on the trifunctional cross linker HATRIC that contains an NHS ester to couple the small molecule, a hydrazone to covalently bind to the carbohydrates of the unknown target proteins at the cell membrane and an azide as pull down function.
The small molecule is coupled to HATRIC using a primary amine. Either your small molecule contains already a primary amine or a primary amine is added by derivatization. In the next step cells expressing the unknown targets and off-targets are mildly oxidized and the HATRIC coupled small molecule is added. The small molecule binds its target(s) at the cell membrane and the second arm of HATRIC covalently binds to the carbohydrates of the target protein(s). During that interaction the cells are still alive. Then the cells are lysed, processed and the third arm of HATRIC is used to pull down the target proteins. Proteins are identified through bottom-up proteomics, relatively quantified and compared to one or several controls. The target candidates are those proteins that are enriched in the ligand of interest samples compared to the control treated samples since the ligand target interaction increases the likelihood of the target carbohydrates to covalently bind to HATRIC compared to the average cell surface protein. Controls can be a positive control such as transferrin or a negative control for example samples treated with an excess of the small molecule devoid of HATRIC prior to adding the HATRIC small molecule conjugate (competition).
Are you interested to identify the mode of action of your small molecule?
Please contact us
Customers Testimonials – LRC-TriCEPS Service
Testimonials from our customers who have used the LRC-TriCEPS technology – in collaboration with Dualsystems Biotech AG.
OncoLille Cancer Institute
Best,
Silvia Gaggero, PhD
Mitra Lab, Inserm
OncoLille Cancer Institute
Lille, France
AstraZeneca
James Dodgson
AstraZeneca
Cambridge, UK.
UCF College of Medicine
Justine Tigno-Aranjuez, Ph.D.
Assistant Professor of Medicine
UCF College of Medicine
Cohbar
Dr. Lindsay Stark
Drug Discovery Scientist at CohBar
Technical University of Munich
Using LRC-TriCEPS, we aimed to identify novel direct cell surface receptors of our ligand of interest.
At any time, we experienced great support of Dualsystems Biotech. They kindly helped to find optimal conditions for our purposes and provided help with any kind of question before, during and after the experiment. LRC-TriCEPS allowed us to identify novel cell surface receptors of our ligand, which we could successfully validate in different cell types and with different biochemical assays. We can fully recommend Dualsystems Biotech and are looking forward to perform further analyses using LRC-TriCEPS.
Prof. Dr. rer. nat. Achim Krüger
Institute of Experimental Oncology and Therapy Research
Klinikum rechts der Isar, Technical University of Munich
University of Miyazaki
Hideyuki Sakoda, MD, PhD
Associate professor
Department of Biological Sciences, Faculty of Medicine, University of Miyazaki, Japan.
Lund University Diabetes Centre
Dr. Claire L. Lyons,
Associate Researcher
Unit of Medical Protein Science
Lund University Diabetes Centre
Sweden
Australian National University
The Australian National University
Co-Director, Centre for Personalised Immunology, NHMRC Centre of Research Excellence
College of Health & Medicine
The Australian National University
Harvard Medical School, Brigham and Women’s Hospital
Maximillian Rogers, PhD
Research Scientist
Harvard Medical School, Brigham and Women's Hospital
Department of Medicine, Cardiovascular Division
Boston, MA
Center for Biomolecular & Cellular Structure, Institute for Basic Science
Associate Professor
Graduate School of Medical Science and Engineering, KAIST
Chief Investigator
Center for Biomolecular & Cellular Structure, Institute for Basic Science (IBS)
Department of Internal Medicine Erasmus MC
Dr Patric Delhanty
Laboratory of Metabolism and Reproduction
Department of Internal Medicine
Erasmus MC
Rotterdam, The Netherlands
Seoul National University
Chung Hwan Cho, Ph. D. candidate
Environmental Health Microbiology Laboratory
Department of Environmental Public Health
Seoul National University
Immuno-Oncology Discovery from Bristol-Myers Squibb published in Nature
Identification of a new immune-oncology drug target using the LRC-TriCEPS platform on primary human T-cells.
The University of Oklahoma – Health Sciences Center
Anne Kasus-Jacobi, PhD
Associate Professor of Research
University of Oklahoma Health Sciences Center
Department of Pharmaceutical Sciences
Oklahoma City, Oklahoma, USA
CuroNZ Ltd
Frank Sieg, PhD
CSO
CuroNZ Ltd
Mangawhai in New Zealand
University of Pittsburgh
Maliha Zahid, M.D., Ph.D.
Assistant Professor
Departement of Developmental Biology
University of Pittsburgh
University of Oklahoma Health Sciences Center
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
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
Hepatic Fibrosis Group
QIMR Berghofer Medical Research Institute, Australia
University of Miami, Miller School of Medicine
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)
Working group from Prof. Dr. med. Luisa Klotz
Münster University Hospital (UKM), Germany
University of Manitoba
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
Assistant Professor of Clinical Investigation
The Rockefeller University
Medizinische Hochschule Hannover
East Tennessee State University
Assistant Professor
East Tennessee State University
Igenica Biotherapeutics
Senior Director, Preclinical Development
Igenica Biotherapeutics
Centro de Estudos de Doenças Crónicas
« 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
University of California San Francisco
Assistant Professor in Residence
University of California San Francisco (UCSF)
LRC-TriCEPS / HATRIC-LRC Publications
Concerning the LRC-TriCEPS or HATRIC-LRC platforms.