The synthesis of 11 cyclic hexapeptides, some of which contain a carbohydrate side chain moiety, is described in this paper. A glycosylamine was coupled without hydroxyl protecting groups either directly or via a butyric acid spacer to the side chain of glutamic acid, leading to beta-N-glycosylated peptides. All peptides described are selective NK-2 antagonists. The binding affinity to the NK-2-receptor ranges from 7 x 10(-7) to 1 x 10(-8) M, whereas at the NK-1 receptor the IC50 was > 10(-5) M with the exception of cyclo(-Lys(Boc)-Trp-Phe-Gly-Leu-D-Leu-) (I), which shows low affinity to the NK-1 receptor (IC50 = 9 x 10(-6) M). The antagonist activity is determined in the hamster trachea assay. pA2-Values range from 7.1 to 7.8. The results demonstrate the broad range of side chains which can be accommodated at the glutamine position without a major drop in activity. The different charges of the lysine and the glutamic acid peptides indicate that the interaction with the receptor at this position is not determined by ionic forces. Rather, we expect that conformational flexibility allows differently charged amino acid residues to be accommodated by the receptor.