Cyclopeptides structure

FIGURE 11.7 Structure of cyclopeptides c(Gly -Pi-oAba-5-CH2X) (9) and c(Gly -Pi-mAba-5-CH2X) (10). 

Reboud-Ravaux, M. Convert, O. Mazaleyrat, J.-P. Wakselman, M. Structural factors in the enzymic hydrolysis of cyclopeptides containing an ortho- or meta-amino benzoic acid residue. Bull. Soc. Chim. Fr. 1988, 267-271. 

Wakselman, M. Mazaleyrat, J.-P. Lin, R. C. Xie, J. Vigier, B. Vilain, A. C. Fesquet, S. Boggetto, N. Reboud-Ravaux, M. Design, synthesis and study of a selective cyclopeptidic mechanism-based inhibitor of human thrombin. In Peptides Chemistry, Structure... 

Complete structural analysis requires mass spectral and NMR data as well as chemical degradation and analysis of the chirality of the constituent amino acids, determination of the mode of linkage of lysine (a- or s-), the size of the cyclopeptide or cyclodepsipeptide ring, etc. (37). In some cases sttuctures have been proposed based only on mass spectral data. Difficulties arising in this approach were discussed (44). To determine the three-dimensional structure an X-ray... 

Molecular modeling studies toward the structural optimization of new cyclopeptide-based HDAC inhibitors modeled on the natural product FR235222. Bioorganic and Medicinal Chemistry, 16, 8635-8642. 

However, this strategy failed when applied to the synthesis of the cyclopeptide lissoclinamide 7. Here, the serine-derived oxazoline moiety could not be selectively thiolyzed in the presence of the threonine-derived oxazoline in the cyclopeptide 334. " The authors attributed this lack of chemoselectivity to the increased stability and thus reduced reactivity, of the serine-derived oxazoline in the macrocyclic scaffold. AU three oxazoline moieties reacted under the prolonged reaction conditions to give the trithio cyclopeptide 335 (Scheme 8.102). The structure of 335 was confirmed by conversion to the tristhiazoline cyclopeptide 336. 

In 1963 a group of Swiss authors (12) isolated zizyphine from Zizyphus oenoplia and recognized isoleucine and proline as components. Two years later Zbiral etal. (13) proposed a complete structure which was later revised (14). Pais et al. (15) in an earlier preliminary report suggested the structure of pandamine which had been isolated from Panda oleosa. This was confirmed in 1966, and the structure of the similarly constituted pandamine was reported (17). Shortly thereafter Tschesche and co-workers (18) reported the structure of an alkaloid of this type scutianine-A from Scutia buxifolia. Since then the number of cyclopeptide alkaloids of known structure has risen to more than sixty, a figure which Klein and Rapoport had envisioned in 1968 (20). The workers at Gif-sur-Yvette and at Bonn have been in the forefront of these researches but others have made important contributions (19-26). 

The zizyphine-A type are 13-membered cyclopeptides composed of / -(2-methoxy-5-hydroxyphenyl)vinylamine, 3-hydroxyproline, and another amino acid. The first known representative was described as zizyphine in 1965 and given an open chain structure (13). It was subsequently renamed zizyphine-A in view of a further examination of Zizyphus oenoplia which disclosed other peptide alkaloids (14). 

Calixarenes provided the main inspiration for the artifidal receptors studied in my group. We wanted to develop a new class of macrocyclic host with binding properties and structural variability similar to calixarenes but a closer relationship to natural systems. The obvious choice was, of course, to base such receptors on cyclopeptides, macrocydic compounds that are composed of the same subunits as the natural systems. 

The starting point of our investigations was a cydic hexapeptide containing 3-aminobenzoic acid and glutamic add-5-isopropyl ester subunits 2 [12]. Our structural assignment showed that this cyclopeptide preferentially adopts conformations... 

This crystal structure shows that the iodide forms hydrogen bonds to all six NH of the two peptide moieties in the complex. It also demonstrates how effectively the anion is embedded between the cyclopeptides. Complex formation thus shields the guest from surrounding solvent molecules, an effect that strengthens receptor-substrate interactions this might be one reason for the anion affinity of 5 in aqueous solution. 

Pronounced shifts of cyclopeptide signals in the XH NMR spectrum caused by adding sodium sulfate to a solution of 28 in D2O/CD3OD 1 1 (v/v) clearly indicated that the anion is bound inside the cage. Force-field calculations provided a picture of the structure of the complex formed, which is stabilized by a well-defined array of hydrogen bonds (Fig. 4). 

Figure 2.18 The tetradecapeptide somatostatin is a nanomolar-to-subnanomolar ligand of five different somatostatin receptor subtypes. Compounds 62-66 are structurally simplified analogs from four combinatorial libraries, with up to 350 000 members per library. Each compound shows a remarkable selectivity against the different sstl-sst5 receptor subtypes (Table 2.1). The orientation of the compounds follows a projection of their superposition with a Merck cyclopeptide.

The mass spectral behavior of the cyclopeptide 438 shows the formation of the azacyclol structure 477 in a mass spectrometer (65ACH(44)93 68ZOB770). 

Zizyphine-F (62 R = H), isolated from Z. oenoplia, is the first example of a cyclopeptide alkaloid bearing a phenolic hydroxy-group as part of the styrylamine unit." Its structure is based upon spectral data and conversion into the known... 

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