Exploitation of the Ornithine Effect Enhances Characterization of Stapled and Cyclic Peptides.

Autor: Crittenden CM; Department of Chemistry, University of Texas, Austin, TX, 78712, USA., Parker WR; Department of Chemistry, University of Texas, Austin, TX, 78712, USA., Jenner ZB; Department of Chemistry and Biochemistry, Southwestern University, Georgetown, TX, 78626, USA., Bruns KA; Department of Chemistry and Biochemistry, Southwestern University, Georgetown, TX, 78626, USA., Akin LD; Department of Chemistry, University of Texas, Austin, TX, 78712, USA., McGee WM; Department of Chemistry, University of Texas, Austin, TX, 78712, USA., Ciccimaro E; Bristol-Myers Squibb, Princeton, NJ, 08543, USA., Brodbelt JS; Department of Chemistry, University of Texas, Austin, TX, 78712, USA. jbrodbelt@cm.utexas.edu.
Jazyk: angličtina
Zdroj: Journal of the American Society for Mass Spectrometry [J Am Soc Mass Spectrom] 2016 May; Vol. 27 (5), pp. 856-63. Date of Electronic Publication: 2016 Feb 10.
DOI: 10.1007/s13361-016-1355-7
Abstrakt: 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.
Databáze: MEDLINE
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