Peptide building blocks

Scheme 12. Synthesis of N-terminal labeled peptide building blocks. DIC diisop-ropylcarbodiimide, HOBt ...

Similarly, iterative NRPSs operate in a linear fashion but utilize at least one domain or module multiple times for the synthesis of a single NRP product. Thus, peptides assembled by iterative synthetases contain short, repeating units of peptide building blocks. In such systems, the terminal PCP-TE (or infrequendy PCP-C) didomain is responsible for both condensation of the repeating peptide units and chain release from the assembly line. NRPs biosynthesized in this manner include enniatin, enterobactin, bacillibactin, " gramicidin and the depsi-peptides valinomycin and cereulide. Of these examples, condensation of the precursor peptides for both enterobactin and gramicidin S has been extensively studied and will be discussed in detail. 

Hirst, A. R. Huang, B. Castelletto, V. Hamley, 1. W. Smith, D. K. Selforganisation in the assembly of gels from mixtures of different dendritic peptide building blocks. Chem. Eur. J. 2007,13, 2180-2188. 

Scheme 23 Synthesis of Cyclic Peptide Building Blocks through End-to-End Cysteine-Thioester Cycliza-tion,87n61...

The formation of two-dimensional nanocrystals, by peptide amphiphiles is also influenced by the chirality of the peptide building block.125 Three types of two-dimensional crystals were observed after the assembly of the functionalized peptide amphiphiles 17-19 shown in Figure 7.11 (above) at the air-water interface, which was followed by polymerization. These two dimensional crystals include (/) a racemic compound, in which each enantiomer is packed with its mirror image in a crystalline order, (it) enantiomorphous conglomerates, in which each enantiomer is segregated into small domains, and (iii) a solid solution, in which all molecules are randomly distributed without crystalline order. Interestingly, in the case of the two-dimensional system arising from the racemic compound,... 

Fig. 4. Scheme of NCL. The mechanism allows the straightforward preparation of small proteins with native backbone structures from fully unprotected synthetic peptide building blocks. The initial tran -thioesterification step includes the chemo-selective reaction between one peptide with a C-terminal a-thioester group (peptide 1) and second peptide with an N-terminal cysteine residue (peptide 2). Generated thio-ester-linked intermediate spontaneously rearranges to form a native peptide bond at the site of ligation. 

Figure 5. Scheme showing the formation of the metal-peptide building block units via complexation of two AQ-Pall4 peptides (cylinders) to a Pt(en) center and their subsequent self-assembly through the formation of a-helical coiled-coils. (Reprinted with permission from reference 6. Copyright 2007 American Chemical Society.)... 

With one major target fully disassembled into four components of reasonable size, simplification of the remaining piece, tripeptide 18, was then achieved in just a few retrosynthetic operations, starting with the removal of its lone aryl chlorine substituent to afford 44 as delineated in Scheme 7. Subsequent removal of one peptide building block (45) from this fragment then revealed dipeptide 46, whose amide group could then be dissected into amine 47 and carboxylic acid 48. 

Having dissected vancomycin aglycon (13) into two major pieces, the simpler of these, tripeptide 50 (Scheme 9), was then disconnected into three peptide building blocks (52, 53, and 54) through... 

Most of the activation methods known from conventional peptide synthesis in solution were explored on polymer concerning their desired reactivity in relation to side reactions, which are particularly unfavorable if the by-products are also bound to the support. Though urethane-masked amino acids generally are shielded from racemization under controlled conditions, this problem limits the use of peptidic building blocks C-terminally activated, since they tend to form the redoubtable oxazolinone intermediate from which the abstraction of a -proton is facilitated (Fig. 40). Recent results indicated a chance to overcome this problem and will be mentioned in the proper section of this chapter. 

Cornille, R, Fobian, Y.M., Slomczynska, U. et al. (1994) Anodic amide oxidations confor-mationally restricted peptide building blocks from direct oxidation of dipeptides. Tetrahedron Letters, 35, 6989-6992. 

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