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Reversible backbone protection enables combinatorial solid-phase ring-closing metathesis reaction (RCM) in peptides.
Niko Schmiedeberg1, Horst Kessler
1Institut für Organische Chemie, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
Organic Letters
|January 5, 2002
Summary
Ring-closing metathesis (RCM) was applied to resin-bound peptides. Optimized protocols involving reversible backbone protection enabled successful RCM cyclization of challenging peptide epitopes.
Area of Science:
- Organic Chemistry
- Peptide Chemistry
- Biotechnology
Background:
- Ring-closing metathesis (RCM) is a powerful tool for macrocycle synthesis.
- Applying RCM to solid-phase peptide synthesis presents challenges, particularly for constrained peptide structures.
Purpose of the Study:
- To investigate the feasibility of RCM for cyclizing resin-bound peptides with olefinic side chains.
- To overcome limitations hindering RCM application in solid-phase peptide synthesis.
Main Methods:
- Utilized ring-closing metathesis (RCM) on resin-bound peptides.
- Introduced reversible backbone protection (Ser(Psi(Me,Me)pro)) to disrupt secondary structures.
- Developed optimized reduction and purification protocols.
Main Results:
- RCM failed on a protein-derived homodetic 10mer peptide epitope without modifications.
- Successful cyclization of RCM peptides was achieved after implementing reversible backbone protection.
- A full set of RCM cyclized peptides was generated using optimized protocols.
Conclusions:
- Reversible backbone protection is crucial for successful RCM cyclization of challenging peptide epitopes on solid phase.
- Optimized RCM protocols can be applied to generate complex cyclic peptides for various applications.