# Late-Stage Modification of Biomolecules via Radical-Based Methods

> **NIH NIH R01** · NEW YORK UNIVERSITY · 2024 · $358,367

## Abstract

Project Summary
Late-stage modification of pharmaceutically relevant small molecules and biomolecules, including alcohols,
peptides, and carbohydrates, is crucial in drug discovery and chemical biology research. However, achieving
selectivity and specificity among the diverse functional groups present within such molecules is a primary
challenge in late-stage functionalization. This proposal aims to address this challenge by leveraging the non-
polar nature of radical intermediates, which exhibit orthogonal reactivity compared to the prevalent polar
functional groups found in biomolecules. Specifically, a phosphoramidite reagent will selectively functionalize
hydroxyl groups by enabling deoxygenative radical formation and incorporate it into various transformations,
including the Giese reaction, cross-coupling, and trifluoromethylation reactions. The mild conditions and
moderate electrophilicity of the phosphoramidite will offer compatibility with biomolecules rich in various
reactive groups. Mechanistic studies of radical capture by nickel intermediates will inform catalyst design for
stereoconvergent deoxygenative coupling of alcohols. Furthermore, understanding this fundamental step will
provide insight for the design of a broader range of cross-coupling reactions involving radical intermediates
generated from various means, including chemical, photoredox, and electrocatalytic activation. Finally, the
proposed research aims to develop novel photoredox electron donor-acceptor coupling reactions that
facilitate the synthesis of cyclic peptides, a promising strategy for drug development. These reactions will
expand the chemical space accessible to drug discovery and facilitate the development of new therapeutic
agents.

## Key facts

- **NIH application ID:** 10826558
- **Project number:** 2R01GM127778-06
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** Tianning Diao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $358,367
- **Award type:** 2
- **Project period:** 2019-04-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10826558

## Citation

> US National Institutes of Health, RePORTER application 10826558, Late-Stage Modification of Biomolecules via Radical-Based Methods (2R01GM127778-06). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10826558. Licensed CC0.

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