# Chemical methods to prepare bioactive cyclic and lassoed peptide therapeutics

> **NIH NIH R35** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $385,000

## Abstract

Project Summary
 This program aims to develop new chemical methods for the practical synthesis of bioactive cyclic and
microcin J25-inspired lasso peptide scaffolds. Cyclic bioactive peptide natural products with oxidative linkages
at tyrosine (Tyr), and other phenolic residues, have inspired our development of residue-selective strategies to
prepare Tyr-linked (poly)cyclic peptides. Developed peptide cyclization methods will immediately support
applications toward constrained antimicrobial peptides. Over the next five years, we will develop strategies to
prepare cyclic/bicyclic peptides and demonstrate their potential as antimicrobial peptide therapeutic leads.
Targeted applications will prepare structure-stabilized antimicrobial peptides with anticipated activity against
multidrug resistant Gram-negative bacteria. This program also outlines an integrated experimental and
computational platform to address the standing challenge of microcin J25-inspired lasso peptide chemical
synthesis. This innovative approach will develop methods to enable reversible cyclization and provide informed
folding stabilization criteria to access synthetic microcin J25-inspired lasso peptides. We will iteratively guide this
process with molecular dynamics simulations to quantify lasso fold stability and probability. Longer term, we
anticipate that developed peptide cyclization and lassoing methods will enable the design and synthesis of novel
peptide therapeutic scaffolds to address challenging human disease targets.

## Key facts

- **NIH application ID:** 10941459
- **Project number:** 1R35GM155457-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Andrew George Roberts
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $385,000
- **Award type:** 1
- **Project period:** 2024-06-14 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941459

## Citation

> US National Institutes of Health, RePORTER application 10941459, Chemical methods to prepare bioactive cyclic and lassoed peptide therapeutics (1R35GM155457-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10941459. Licensed CC0.

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