# Protein Domain Mimics as Modulators of Biomolecular Interactions

> **NIH NIH R35** · NEW YORK UNIVERSITY · 2020 · $640,088

## Abstract

Abstract
Interactions of proteins with other biomolecules regulate fundamental cellular events and
misregulation of these interactions leads to disease states. Proteins often utilize small folded
domains for recognition of other biomolecules. The basic hypothesis guiding our research is that
by mimicking these folded domains we can specifically inhibit chosen complex formation with
rationally designed synthetic molecules. Based on this hypothesis, we have developed several
classes of Protein Domain Mimics (PDMs) that faithfully reproduce structural epitopes on protein
surfaces. This work has created a foundation for the development of a new class of structure–
based therapeutics. Our efforts so far have focused on mimicry of a natural binding partner to
inhibit complex formation. A challenge with this approach is that natural protein-protein
interactions are often transient and characterized by weak binding affinities. Mimicry of one
partner, therefore, often also leads to weak binders, which are undesirable as inhibitors of
complex pathways in the cellular context. A new approach is, therefore, required for rational
design of protein based binders that does not begin with natural complexes. In this NIGMS MIRA
proposal, we aim to develop new starting points for PDM design by utilizing secondary and tertiary
structure-grafted protein displays for high affinity sequences. We will apply the new strategy to
target therapeutically important protein-protein interactions for which there are no potent inhibitors,
including intrinsically disordered proteins. Studies in each Aim will advance general approaches
to inhibit protein-protein interactions, and establish PDMs as distinct constructs spanning the
molecular size space between small molecules and proteins.

## Key facts

- **NIH application ID:** 9857043
- **Project number:** 5R35GM130333-02
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Paramjit S Arora
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $640,088
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9857043

## Citation

> US National Institutes of Health, RePORTER application 9857043, Protein Domain Mimics as Modulators of Biomolecular Interactions (5R35GM130333-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9857043. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*