AbstractThe conformational properties in DMSO of two head‐to‐tail cyclic analogues of kallidin ([Lys0]‐bradykinin, KL) as well as those of the corresponding linear peptides were studied by NMR and molecular dynamics (MD) simulations. The modifications in the sequence were introduced at position 6, resulting in the four peptides, [Tyr6]‐KL (YKL), [Trp6]‐KL (WKL), cyclo‐([Tyr6]‐KL) (YCKL) and cyclo‐([Trp6]‐KL) (WCKL).The linearWKLanalogue was significantly more potent than kallidin on rat duodenum preparations, whereasYKLwas significantly less potent. Both cyclic peptides,YCKLandWCKLdisplayed similar activity, lower than that of the linear analogues and also of cyclo‐KL.The two linear analogues display high conformational flexibility in DMSO. In the predominant conformer, for both peptides, all three X‐Pro bonds adopt atransconfiguration. Three out of four conformers present inYCKLandWCKLwere completely assigned. The configurations at the X‐Pro bonds are the same for the two analogues. All cyclic conformers show acisconfiguration in at least one X‐Pro bond and always opposite configuration for the two consecutive X‐Pro bonds.The NOE‐restrained MD calculations resulted in the detection of several elements of secondary structure in each of the conformers. Such elements are described and their possible relevance to biological activity is discussed. Copyright © 2004 European Peptide So