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Related Experiment Video

Updated: Jun 30, 2026

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water

Published on: August 2, 2012

A Scalable Design for Proximity-Inducing Molecules.

Endri Karaj^1,2, Varsha Venkatarangan^1,3,4,2, Shaimaa H Sindi^1,2

¹Chemical Biology and Therapeutics Science, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Biorxiv : the Preprint Server for Biology

|February 27, 2026

Summary

This summary is machine-generated.

We developed GRoup-transfer chimeras for Inducing Proximity (GRIPs), a scalable platform for modifying proteins. GRIPs utilize abundant effector inhibitors to precisely edit post-translational modifications (PTMs) for new therapeutic applications.

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Last Updated: Jun 30, 2026

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water

Controlling the Size, Shape and Stability of Supramolecular Polymers in Water

Published on: August 2, 2012

Scalable Nanohelices for Predictive Studies and Enhanced 3D Visualization

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Generating Controlled, Dynamic Chemical Landscapes to Study Microbial Behavior

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Published on: January 31, 2020

Area of Science:

Biochemistry
Chemical Biology
Molecular Biology

Background:

Chimeric molecules, like PROTACs, enable targeted protein modification by linking effector enzymes with proteins-of-interest (POIs).
Current chimera technologies face scalability limitations due to reliance on rare, non-inhibitory effector binders.

Purpose of the Study:

To develop a scalable and versatile platform for protein post-translational modification (PTM) editing.
To engineer novel chimeras using abundant effector inhibitors for enhanced therapeutic applications.

Main Methods:

Development of GRoup-transfer chimeras for Inducing Proximity (GRIPs) using effector inhibitors and group-transfer handles.
Creation of 6 GRIPs classes across 3 PTMs, testing 16 effector-POI pairs, and a toolbox of 42 group-transfer handles.
Utilizing global proteomics to confirm specificity and employing GRIPs in endogenous and tagged protein systems.

Main Results:

Demonstrated scalability of GRIPs across diverse PTMs and effector-POI pairs.
Confirmed specificity of group transfer and PTM editing via proteomics.
Showcased novel functionalities including sustained inhibition, prevention of rebound signaling, and pathway activation in endogenous systems.
Achieved condensate formation, pathogenic PTM clearance, and PTM crosstalk initiation in hemi-endogenous systems.

Conclusions:

GRIPs offer a scalable and adaptable platform for precise PTM editing.
This technology enables new therapeutic strategies by imparting novel functionalities to POI drugs.
GRIPs advance the field of targeted protein modification with broad applicability.