# Development and Applications of Bioorthogonal Chemistry: Administrative Supplement for Equipment

> **NIH NIH R35** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $145,555

## Abstract

Development and Applications of Bioorthogonal Chemistry: Administrative Supplement for Equipment
ABSTRACT
We have a long-standing interest in developing reactivity-based chemical tools to address significant biological
problems that are difficult to solve using conventional molecular biology techniques. In our original MIRA
application, we plan to continue our studies of orthogonal chemical reactivity at the chemistry-biology interface
and pursue the following two related projects. In Project 1, we will construct the FRET-based biosensors of
GLP-1R and GCGR using bioorthogonal chemistry techniques. These biosensors will then be employed to
probe the conformational dynamics during the ligand-induced receptor activation and signaling in live cells. A
new set of fluorescence ‘turn-on’ reagents will be designed for bioorthogonal labeling of the intracellular loop 3
of GLP-1R and GCGR to allow single-cell intra- and inter-molecular FRET analysis of receptor dynamics in live
cells. In Project 2, we will develop genetically encoded chemical crosslinker containing an alkyne group and
apply this chemical crosslinker to map the time-dependent GLP-1R and -arrestins interactomes by mass
spectrometry in response to ligand stimulation. We expect that these studies will validate new bioorthogonal
tools for real-time monitoring of protein conformation and protein-protein interactions in live cells. Also, we will
gain novel insights into the GLP-1R and GCGR activation dynamics and structural basis of biased signaling
that are crucial for the development of targeted therapies for the treatment of diabetes and obesity. This
Administrative Supplement requests the acquisition of an Agilent QTOF 6530B LC/MS system, which
would allow us to characterize the incorporation of chemical crosslinkers into recombinant proteins with higher
mass accuracy and throughput and significantly accelerate the discovery of the GLP-1R and -arrestins
interactomes by mass spectrometry as described in Project 2.

## Key facts

- **NIH application ID:** 10132024
- **Project number:** 3R35GM130307-02S1
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Qing Lin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $145,555
- **Award type:** 3
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132024

## Citation

> US National Institutes of Health, RePORTER application 10132024, Development and Applications of Bioorthogonal Chemistry: Administrative Supplement for Equipment (3R35GM130307-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10132024. Licensed CC0.

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