# Protein-Induced Self-Assembly and Disassembly of Nanostructures Based on Oligo

> **NIH NIH R35** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2021 · $513,034

## Abstract

PROJECT SUMMARY / ABSTRACT
 This proposal describes a concerted approach to the design, synthesis, and study of novel self-
assembling molecules that are responsive to specific proteins. We take two complementary approaches. First,
we develop design guidelines where proteins act as the trigger to deconstruct a higher order assembly to a
lower order one (protein-responsive supramolecular disassembly). In this process, the assemblies transform
from an effective host for hydrophobic small molecules to an ineffective one, which has implications in
developing precise therapeutic responses to protein imbalances. In the second approach, we propose to
develop molecular design guidelines that program a non-assembling polymer to transform into a higher order
assembly in response to proteins (protein-templated self-assembly). The resultant nanoassemblies are
programmed to release these encapsulated proteins in their pristine form in the presence of a specific
biologically-relevant stimulus or due to a combination of such stimuli. Such a strategy will offer the ability to
traffic proteins across a cellular membrane and release them inside cells, which has implications in several
unmet challenges in biomedicine.
 In the protein-responsive supramolecular disassembly approach, we propose to develop versatile
supramolecular assemblies that disassemble in response to specific proteins as stimuli. There have been
great advances in stimuli-sensitive supramolecular assemblies. However, these have primarily focused on
systems that respond to changes in factors such as pH, temperature, or redox conditions, which are
secondary imbalances in biology. The most direct and primary indicator of imbalance in biology involves
change in protein activity. Therefore, generating supramolecular assemblies that respond to proteins is
exciting. Our primary objective is to obtain a better understanding of the structural factors that control the
assembly/disassembly events in response to specific combinations of enzymatic and non-enzymatic proteins.
 In the protein-templated self-assembly approach, the templating proteins are incarcerated as guests into
a matrix of host polymers. The resultant nanoassemblies are programmed to release these encapsulated
proteins in their pristine form in the presence of a specific biologically-relevant stimulus or due to a
combination of such stimuli. A key goal of the proposed research is to develop this into a new supramolecular
platform that is useful for a broad range of soluble proteins, a capability that does not currently exist. The
primary premise of the proposed research then is to develop a fundamental framework for custom-designing
such supramolecular assemblies that can predictably encapsulate a protein, turn its function off, protect it
from denaturation in non-native environments, and regain its native structure and function in response to a
stimulus that is specific to the target environment. We will identify the structural factors that ...

## Key facts

- **NIH application ID:** 10126879
- **Project number:** 5R35GM136395-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Sankaran Thayumanavan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $513,034
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126879

## Citation

> US National Institutes of Health, RePORTER application 10126879, Protein-Induced Self-Assembly and Disassembly of Nanostructures Based on Oligo (5R35GM136395-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10126879. Licensed CC0.

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