Octapeptides, cyclic, conformations

WM Kazmierski, RD Ferguson, RJ Knapp, GK Lui, HI Yamamura, VJ Hruby. Reduced peptide bond cyclic somatosatin based opioid octapeptides. Synthesis, conformational properties and pharmacological characterization. Int J Pept Protein Res 39 401 114, 1992. 

The spectral data of the patellamides was also reasssigned and the new assignments used for elucidation of the structures of three new metabolites, the octapeptide prepatellamide B formate (24) and the heptapeptides, prelissoclinamide 2 (25), and preulicyclamide (26) [58]. The molecular conformation of patellamide A (21) was determined by X-ray crystallography [59,60] and the solution conformations of patellamides B (22) and C (23) were determined by NMR spectroscopy and molecular dynamics [61]. The octapeptide preulithiacyclamide (27) is a potent inhibitor of Macrophage Scavenger Receptor and was isolated from L. patella from Palau along with other known cyclic peptides [62],... 

Examples of the way these two entirely different approaches compliment each other are developing in conformation studies with the hormones angiotensin, oxytocin, and vasopressin. In 1964 Craig, Harfenist, and Paladini (7) published the comparative half-escape times shown in Table I in 0.01N acetic acid and another series in Table II using a different membrane less porous and not as selective as the first. Oxytocin and vasopressin are cyclic octapeptides with an S-S linkage closing the ring at the 1-6 positions (5, 6). Their size is thus limited except for the side... 

The hard-sphere potential has also been used to compute the sterically allowed conformations of small polypeptides of known amino acid sequence, viz. an octapeptide loop of ribonuclease (Nemethy and Scheraga, 1965) and the cyclic decapeptide gramicidin-S (Vanderkooi et al., 1966). We shall use the calculation for gramicidin-S to illustrate the method. This decapeptide consists of two identical pentapeptides joined into a ring by peptide bonds, the amino acid sequence being... 

Gramicidin-S, cyclo[(Orn-Leu-D-Phe-Pro-Val)2], is a C2-symmetric, antibacterial, cyclic decapeptide. Structural studies have shown that the peptide conformation consists of two type IP p-turns with a connecting p-sheet. Based on molecular modeling studies and the results from earlier experimental studies of cyclic octapeptides, Ripka et al. at DuPont Merck Pharmaceuticals believed that the four amino acids that make up one of the p-turns could be replaced by a benzodiazepine (BZD) moiety. These authors designed the gramicidin-S analogue cyclo(Lys-Leu-D-Phe-Pro-Val-Lys-BZD) (95) based on... 

We are interested in using cyclic peptides for the template molecule, because allosteric proteins can be synthesized by utilizing conformational change of the cyclic peptide upon complexation with a metal ion [5]. In the present study, two basic a-helical peptides, which mimic transcriptional regulator proteins binding to DNA, were synthesized and connected to a cyclic octapeptide template. 

Cusack, R.M., Grondahl, L Abbenante, G Eairlie, D.P., Gahan, LR., Hanson, G.R., and Hambley, T.W. (2000) Conformations of cyclic octapeptides and the influence of heterocyclic ring constraints upon calcium binding./. Chem. Soc. Perkin Trans. I, 323-331. 

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