# Platforms for the Synthesis of Bacterial Protein Synthesis Inhibitors

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $111,826

## Abstract

Due to the increasing prevalence of antimicrobial resistance and the paucity of antibiotics in the pipeline, there
is a pressing need for new methods to bolster the armamentarium of antimicrobial therapeutics. The goal of our
NIH R35 award is to develop antibiotic candidates using as templates natural and synthetic molecules that inhibit
the bacterial ribosome. These candidates, accessible through novel chemical approaches, have the potential to
overcome the limitations of previous classes of protein synthesis inhibitors.
During ≤2 years of support, we have:
• Developed the first synthesis of seco-lankacidinols and reassigned the structure of 2,18-secolankacidinol
B (Angew. Chem. Int. Ed 2018, 57, 13551-13554)
• Designed an improved, organotin-free synthesis of streptogramin antibiotics (Tetrahedron 2019, 75,
3309-3318)
• Reassigned the structure of iso-lankacidinol by means of a modular, fully synthetic route (submitted)
• Synthesized >100 streptogramin analogs, tested each of them in >20 strains of bacteria, characterized
mechanisms with CryoEM, and discovered analogs that overcome resistance (submitted, see preprint at
ChemRXiv, doi: 10.26434/chemrxiv.8346107.v2)
• Developed a late-stage C–H amination strategy to epi-lankacidins (manuscript prepared, submission
anticipated April 2020)
• Prepared >20 candidates for binding-induced hybridization
All of the primary goals of our R35 award are reliant on a workhorse LCMS system that can accurately and
rapidly analyze small molecules in reaction mixtures and in crude biological samples.

## Key facts

- **NIH application ID:** 10135606
- **Project number:** 3R35GM128656-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Ian Bass Seiple
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $111,826
- **Award type:** 3
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135606

## Citation

> US National Institutes of Health, RePORTER application 10135606, Platforms for the Synthesis of Bacterial Protein Synthesis Inhibitors (3R35GM128656-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135606. Licensed CC0.

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