title: Exploitation of the Ornithine Effect Enhances Characterization of Stapled and Cyclic Peptides.
abstract: A method to facilitate the characterization of stapled or cyclic peptides is reported via an arginine-selective derivatization strategy coupled with MS/MS analysis. Arginine residues are converted to ornithine residues through a deguanidination reaction that installs a highly selectively cleavable site in peptides. Upon activation by CID or UVPD, the ornithine residue cyclizes to promote cleavage of the adjacent amide bond. This Arg-specific process offers a unique strategy for site-selective ring opening of stapled and cyclic peptides. Upon activation of each derivatized peptide, site-specific backbone cleavage at the ornithine residue results in two complementary products: the lactam ring-containing portion of the peptide and the amine-containing portion. The deguanidination process not only provides a specific marker site that initiates fragmentation of the peptide but also offers a means to unlock the staple and differentiate isobaric stapled peptides.
authors: Department of Chemistry, University of Texas, Austin, TX, 78712, USA.
authors: Christopher M
authors: CM
authors: Crittenden
authors: Department of Chemistry, University of Texas, Austin, TX, 78712, USA.
authors: W Ryan
authors: WR
authors: Parker
authors: Department of Chemistry and Biochemistry, Southwestern University, Georgetown, TX, 78626, USA.
authors: Zachary B
authors: ZB
authors: Jenner
authors: Department of Chemistry and Biochemistry, Southwestern University, Georgetown, TX, 78626, USA.
authors: Kerry A
authors: KA
authors: Bruns
authors: Department of Chemistry, University of Texas, Austin, TX, 78712, USA.
authors: Lucas D
authors: LD
authors: Akin
authors: Department of Chemistry, University of Texas, Austin, TX, 78712, USA.
authors: William M
authors: WM
authors: McGee
authors: Bristol-Myers Squibb, Princeton, NJ, 08543, USA.
authors: Eugene
authors: E
authors: Ciccimaro
authors: Department of Chemistry, University of Texas, Austin, TX, 78712, USA. jbrodbelt@cm.utexas.edu.
authors: Jennifer S
authors: JS
authors: Brodbelt
mesh_terms: D001120:Arginine / Q000737:chemistry; D009952:Ornithine / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000032:analysis* / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010456:Peptides, Cyclic; D001120:Arginine; D009952:Ornithine
keywords: Cyclic peptide; Ornithine effect; Stapled peptide