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Solid Phase Synthesis of a Functionalized Bis-Peptide Using "Safety Catch" Methodology
Published on: May 15, 2012
Synthesis and solid-phase application of suitably protected gamma-hydroxyvaline building blocks
Mare Cudic1, Frank Marí, Gregg B Fields
1Department of Chemistry & Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USA.
The Journal of Organic Chemistry
|June 23, 2007
Summary
Researchers synthesized gamma-hydroxy-D-valine (D-Hyv), a novel modified amino acid found in conopeptides. This new method enables the creation of D-Hyv-containing peptides for further biological study.
Area of Science:
- Organic Chemistry
- Peptide Chemistry
- Biochemistry
Background:
- The discovery of gamma-hydroxy-D-valine (D-Hyv) in conopeptides presents a challenge for synthetic chemists.
- Understanding the biological roles of modified amino acids like D-Hyv requires efficient synthesis of these building blocks.
Purpose of the Study:
- To develop a robust synthetic route for producing functionalized D-Hyv building blocks.
- To enable the synthesis of D-Hyv-containing conopeptides for biological investigation.
Main Methods:
- Synthesis of D-Hyv from D-Val using an oxidative method.
- Protection of D-Hyv hydroxyl group as TBDMS ether.
- Development of a method for complex disruption using Chelex 110 resin.
- Coupling of protected D-Hyv with Fmoc-OSu for solid-phase peptide synthesis.
Main Results:
- Successful synthesis of Fmoc-D-Hyv(O-TBDMS) in 26% yield from D-Val.
- Separation of diastereomers via preparative RP-HPLC, yielding 13% of Fmoc-D-Hyv(O-TBDMS).
- Synthesis of the conopeptide gld-V* using the developed Fmoc-D-Hyv building block, confirmed by mass and NMR spectroscopy.
Conclusions:
- A practical synthetic methodology for D-Hyv building blocks has been established.
- This approach facilitates the study of hydroxylated conopeptides and their biological functions.
- The synthetic route supports research into oxidative stress effects on proteins.
