The chemical ligation of selectively S-acylated cysteine peptides to form  native peptides via 5-, 11- and 14-membered cyclic transition states.
Cysteine and C-terminal cysteine peptides are selectively S-acylated at 0-20 degrees C by N-(Pg-alpha-aminoacyl)benzotriazoles to give N-Pg-S-acyl-isodi-, -isotri-, and -isotetra-peptides isolated in good yields. N-Fmoc-S-acyl-isopeptides are Fmoc deprotected to afford free S-acyl-isopeptides isolated in high yields. S-Acyl-isodi-, S-acyl-isotetra-, and S-acyl-isopentapeptides undergo chemical ligation; migration of the cysteine S-acyl groups to the N-terminal amino acids via 5-, 11-, and 14-membered transition states giving the corresponding native di-, tetra-, and penta-peptides. By contrast, the Sacyl-isotripeptide prefers intermolecular acylation from one molecule to another over an 8-membered intramolecular transition state. The developed methodology allows convenient isolation of stable, unprotected S-acyl cysteine peptides including the first isolation of S-acyl-isopeptides, which should facilitate the investigation of ligation by physical organic chemistry techniques.
Katritzky
Alan R
AR
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA. katritzky@chem.ufl.edu
Abo-Dya
Nader E
NE
Tala
Srinivasa R
SR
Abdel-Samii
Zakaria K
ZK
D000215:Acylation; D003545:Cysteine / Q000737:chemistry*; D006878:Hydroxides / Q000737:chemistry; D008872:Microwaves; D010456:Peptides, Cyclic / Q000737:chemistry*; D013379:Substrate Specificity; D013455:Sulfur / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry
D006878:Hydroxides; D010456:Peptides, Cyclic; D014230:Triazoles; D013455:Sulfur; C031356:hydroxide ion; D003545:Cysteine