In this paper, we report the difficult synthesis of cyclo(Leu-Pro-Leu-Pro). While the cyclization of Leu-Pro-Leu-D-Pro did not cause problems, the all-L-peptide afforded cyclodimer rather than cyclotetrapeptide (cyclomonomer). A first attempt using our reversible backbone substitution methodology failed. However, we were successful in obtaining the desired cyclo(Leu-Pro-Leu-Pro) by decreasing the concentration. The ratio of cyclomonomer to cyclodimer was raised to 1:1.1 using BOP and 1:0.6 using HATU under our high dilution condition. The structures of the cyclopeptides were confidently assigned by electrospray ionization mass spectrometry and NMR. Copyright (C) 2000 European Peptide Society and John Wiley & Sons. Ltd.
All-L-Leu-Pro-Leu-Pro: A challenging cyclization
El Haddadi, M.; Cavelier, F.; Vives, E.; Azmani, A.; Verducci, J.; Martinez, J.
Journal of Peptide Science
2000-11 / vol 6 / pages 560-570
conformation; cyclization; cyclotetrapeptides; high dilution; peptides; reagents; ring-closure reaction