# Strategies for N to C solid-phase peptide synthesis

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $300,462

## Abstract

PROJECT SUMMARY
 Peptide based pharmaceuticals are becoming increasingly prevalent in late-stage clinical
trials and FDA approvals. Peptide synthesis is traditionally performed in the C to N direction on
solid supports. Peptide synthesis in the N to C direction would enable new opportunities to
improve peptide purity and yield because it will avoid side reactions that plague C to N SPPS
and potentially alter the aggregation state of the peptide during its assembly. However,
challenges such as oxazalone formation and diketopiperazine formation have long prevented
the implementation of such an approach. The long-term objective of this program of research is
to facilitate the synthesis of complex biologically active polypeptides. The objective of this
application is to establish a platform for N to C SPPS that avoids the problematic hurdles of
epimerization caused by oxazalone formation and peptide truncation due to diketopiperazine
formation. We will achieve this objective by employing a mild carbonyl activation strategy that
enable N to C SPPS without causing these undesirable side reactions. We will develop
specialized methods to address slow reactions, challenging sequences, and unique functional
groups that are important to the preparation of biologically active peptides. We will establish the
compatibility of these methods with state-of-the-art SPPS technologies such as microwave and
flow methods. Consistent with the mission of the NIH’s National Institute of General Medical
Sciences, this basic research will ultimately facilitate developments in the study of biological
processes. Furthermore, this research meets the objectives of the Focused Technology
Research and Development Program because the specific aims focus on the technical
challenges and milestones associated with implementing our innovative strategy for peptide
synthesis. If successful, the proposed chemistry will advance biomedical research by positively
impacting all fields where synthetic peptides are needed.

## Key facts

- **NIH application ID:** 9993591
- **Project number:** 5R01GM129475-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Jennifer Lynn Stockdill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,462
- **Award type:** 5
- **Project period:** 2019-08-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993591

## Citation

> US National Institutes of Health, RePORTER application 9993591, Strategies for N to C solid-phase peptide synthesis (5R01GM129475-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993591. Licensed CC0.

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