Solid phase synthesis of cyclic peptides: model studies involving i- (i+4) side chain-to-side chain cyclisation
Cavallaro, V.; Thompson, P.; Hearn, M.
Journal of Peptide Science An Official Publication of the European Peptide Society 4(5): 335-343
ISSN/ISBN: 1075-2617 PMID: 9753393 DOI: 10.1002/(sici)1099-1387(199808)4:5<335::aid-psc155>3.0.co;2-#
Conditions for the synthesis of i-(i + 4) side chain-to-side chain head-to-tail Lys-->Glu and Glu-->Lys linked cyclic peptides related to hypoglycaemic analogues of human growth hormone hGH [6-13] have been examined. The success of the cyclisation reaction with the corresponding resin-bound, partially protected linear peptides was found to be both reagent as well as sequence dependent, with competing inter-chain oligomerisation predominating in some cases. The results also indicated that protection with the bulky Fmoc group of the amino acid residues immediately adjacent to the side chain-deprotected Lys and Glu residues, which participate in the cyclisation reaction, enhanced the rate of lactam formation.