Cyclic-peptide template

In Fmoc chemistry, Lys and Om are conveniently blocked with the Boc protecting group [155]. For more temporary protection, the l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) protecting group is useful in the preparation of branched peptides, multiple antigenic peptides (MAPs), cyclic peptides, template-assembled synthetic proteins (TASPs), and templates for combinatorial chemistry [156-161]. Dde is quasi-orthogonal because the use of dilute hydrazine to cleave Dde partially removes the A -... 

Fig. 7i-iii Helix-sheet-nanofibre transitions of a 4-helix bundle (pH 4) from an a-helix (i 1) to 3io-helix (i 2) to P-strand (i 3) to f-sheet (ii 4-6) and finally to mature fibrils (iii), for four equivalents of H-[AEQLLQEAEQLLQEL]-NH2 covalently tethered to a cyclic peptide template. Arrows show the direction of change over time. Images taken from Singh et al. (Y. Singh, P.C. Sharpe, A.W. McDowall, D.P. Fairlie, submitted), some spectra were removed for easy interpretation. Figures illustrated and modified with Prism4 (version 4.0b, GraphPad)... 

Design and properties of functional nanotubes from the self-assembly of cyclic peptide templates 12CSR6023. 

Eichler, J., Lucka, A.W. and Houghten, R.A., Cyclic peptide template combinatorial libraries Synthesis and identification of chymotrypsin inhibitors. Peptide Res., 7 (1994) 300-307. 

The structures of synthetic peptides used in the present investigation are shown in Fig. 1. Two amphiphilic a-helical peptide chains containing Lys residues were connected to cyclic octapeptide. The association of two peptide chains should be promoted by the presence of cyclic-peptide template. In addition, two amphiphilic peptide chains are stabilized in water with the hydrophobic surfaces facing each other. The arrangements of hydrophobic and hydrophilic residues are shown as helical wheels in Fig. 2. The... 

CD spectra of CHI and CH2 in trimethyl phosphate are shown in Fig. 5, which indicate a -helical conformation without significant interaction between the helices. The helix contents of CHI and CH2 were 97 % and 55 %, respectively, from the ellipticities at 222 nm. The reduction of the helix content in CH2 is presumably because the plane of the cyclic-peptide template is not big enough to accommodate two helices in assembly. The negative ellipticities of CHI and CH2 decreased in a buffer solution as compared with those in trimethyl phosphate (Fig. 6). However, the extent of decreasing ellipticity... 

Recent examples of successful peptide-ligand based discoveries of drug-like peptidomimetics include the discovery of SST antagonists, or the discovery of non-peptidic antagonists of the recently deorphanized urotensin II receptor at Sanofi-Aventis. ° As illustrated in Fig. 3, Flohr etal. used 3D models of the NMR solution structure of cyclic peptide derivatives of Urotensin II as a template for virtual 3D pharmacophore searches which resulted into non-peptidic candidates for lead optimization. 

Scheme 6 m-Amb as a Template to Induce a Loop Conformation in a Cyclic Peptide 69-72 ... 

Scheme 2 Examples of Topological Templates Cyclic Peptides, 14171 Porphyrins,129-301 Cyclodextrins, 281 Calix-arenes131-321...

Another versatile chemoselective ligation method for the efficient synthesis of TASP[98] molecules is based on the rapid and selective reaction of thiols with activated double bonds, e.g. in a maleimide group (Scheme 17).[106-108] For this purpose, the cyclic decameric template is functionalized with four maleimide residues, which allow reaction with thiol-containing peptide fragments in aqueous solution. 

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