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Conformational studies of three agonists of V2 receptor modified with 1-aminocyclohexane-1-carboxylic acid (Acc), [Acc2,DArg8]VP, [Acc3]AVP and [Cpa1,Acc3]AVP, using 2D NMR and theoretical calculations are presented in this paper. It is believed that α, α-disubstituted amino acids, such as Acc, affect the formation of either 310 or α-helical conformation. Moreover, a peptide with Acc may adopt either the γ- or an inverse γ-turn over it. Thus, incorporation of Acc into the arginine-vasopressin sequence induced C7-membered ring conformation with Acc at the top of it, and additional formation of β-bend involving residues in the 2–5 fragment of the peptides. Furthermore, the analogues are also characterized by type I of β-turn involving residues Acc3-Cys6 in [Acc3]AVP and [Cpa1,Acc3]AVP, and by type IV or II′ in [Acc2,DArg8]VP. Replacement of Tyr at position 2 of [Acc2,DArg8]VP with Acc afforded a hydrogen bond between the guanidine moiety of DArg8 and the side chain of either Asn5 or Gln4. In the remaining analogues, the β-turn comprising the Cys6-Gly9 residues allows the positively charged side chain of Arg8 to be directed toward Tyr2. The substitution of Cys1 with Cpa1 enhances hydrophobic properties of N-terminal part of the molecule strengthening thereby the affinity to the binding pocket of receptors. [ABSTRACT FROM AUTHOR]

Copper, cobalt, nickel and zinc chloride complexes with sparteine and 2-methylsparteine were synthesised. The 1:1 metal:sparteine stoichiometry was confirmed by elemental analysis and mass spectra. Absorption spectra of the solids were studied in the IR, and their diffuse-reflectance spectra in the UV–Vis and the NIR spectral range. The spectra obtained are similar to previous results obtained in solutions, suggesting that the metal ion coordination sphere in solution remains the same as in the crystal lattice, with the sparteine and 2-methylsparteine assuming the folded all-chair conformation with trans A–B and cis C–D rings and both nitrogen atoms coordinated with the metal. The structure was confirmed by NMR and X-ray diffraction data, and compared to that of other similar complexes. [Copyright &y& Elsevier]

Trypsin inhibitor SFTI-1 is the smallest and the most potent among BBI inhibitors. It is also an interesting object for SAR studies since it is cyclic 14 amino acid molecule which additionally contains disulfide bridge. We showed that elimination of head-to-tail cycliztion did not influence its activity. Moreover peptoid monomers of Nlys and Nphe introduced in the substrate specificity P 1 position of monocyclic SFTI-1 preserved trypsin and chymotripsin inhibitory activity respectively and made P 1 –P 1 ′ bond proteolytically stable. These findings motivated us to perform conformational analysis of [Nphe 5 ]SFTI-1 by means of 2D NMR spectroscopy and molecular dynamics calculations. Obtained structure occurred to be in a good agreement with published structures for wild-type SFTI-1, its monocyclic analog with disulfide bridge only as well as one containing Nlys peptoid monomer in P 1 position. [ABSTRACT FROM AUTHOR]