Summary:
Scientists at Westlake University have developed a groundbreaking method for sequencing D-proteins, which are mirror-image counterparts to naturally occurring L-chiral peptides and proteins. Traditional sequencing methods, reliant on digestion by site-specific enzymes, don’t work for D-proteins. The team synthesized a mirror-image version of the protein-digesting enzyme trypsin using solid-phase peptide synthesis and native chemical ligation. This novel method enables the analysis of mirror-image proteins, potentially advancing the development of biostable D-peptide drugs.
Key Findings:
- Method Innovation:
- Synthesized a mirror-image trypsin to digest D-peptide bonds, overcoming limitations of traditional sequencing methods.
- Used solid-phase peptide synthesis and native chemical ligation for the innovative approach.
- Sequencing Success:
- Successfully sequenced mirror-image proteins, including a ribosomal protein and a DNA polymerase.
- Provides a crucial analytical tool for evaluating the quality of synthesized proteins.
- Potential Therapeutic Impact:
- D-proteins, being biostable and avoiding natural enzyme recognition, hold promise for drug development.
- Enzyme’s ability to digest D-proteins facilitates the validation of mirror-image ribosome assembly.
- Future Outlook:
- The method may aid the rapid development of mirror-image, D-protein molecules as human therapeutics.
- Ambitious goals include realizing mirror-image translation by synthesizing a mirror-image ribosome.
- Expert Insights:
- Michael Kay highlights the need for appropriate analytical tools in the growing field of mirror-image proteins.
- Stephen Kent acknowledges the ambitious goal of building a mirror-image ribosome, suggesting the field may be getting closer to achieving it.
The breakthrough method for sequencing D-proteins opens new possibilities for the development of mirror-image therapeutics and provides a crucial analytical tool for the evolving field of mirror-image molecular biology.