TY - JOUR
T1 - The chemical ligation of selectively S-acylated cysteine peptides to form native peptides via 5-, 11- and 14-membered cyclic transition states
AU - Katritzky, Alan R.
AU - Abo-Dya, Nader E.
AU - Tala, Srinivasa R.
AU - Abdel-Samii, Zakaria K.
PY - 2010
Y1 - 2010
N2 - Cysteine and C-terminal cysteine peptides are selectively S-acylated at 0-20 °C by N-(Pg-α-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-isopenta-peptides 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 S-acyl-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.
AB - Cysteine and C-terminal cysteine peptides are selectively S-acylated at 0-20 °C by N-(Pg-α-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-isopenta-peptides 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 S-acyl-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.
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U2 - 10.1039/c003234d
DO - 10.1039/c003234d
M3 - Article
C2 - 20372743
AN - SCOPUS:77952364392
SN - 1477-0520
VL - 8
SP - 2316
EP - 2319
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 10
ER -