Cyclic and Lasso Peptides: Sequence Determination, Topology Analysis, and Rotaxane Formation. Issue 21 (27th April 2018)

• Record Type: Journal Article
• Authors: Elashal, Hader E.; Cohen, Ryan D.; Elashal, Heidi E.; Zong, Chuhan; Link, A. James; Raj, Monika
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 21(2018)
• Page Start: 6150
• Page End: 6154
• Publication Date: 2018-04-27
• Subjects: peptides -- rotaxanes -- sequencing; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201801299
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A broadly applicable chemical cleavage methodology to facilitate MS/MS sequencing was developed for macrocyclic and lasso peptides, which hold promise as exciting new therapeutics. Existing methods such as Edman degradation, CNBr cleavage, and enzymatic digestion are either limited in scope or completely fail in cleavage of constrained nonribosomal peptides. Importantly, the new method was utilized for synthesizing a unique peptide‐based rotaxane (both cyclic and threaded) from the lasso peptide, benenodin‐1 ΔC5. Abstract : Making the cut : Macrocyclic and lasso peptides can be sequenced by site‐selective chemical cleavage and subsequent analysis by tandem mass spectrometry. This strategy was also used to synthesize unique peptide‐based rotaxanes (both cyclic and threaded) from the lasso peptide benenodin‐1 ΔC5.