C- and N-termini

The solution methods require orthogonal protection of the C- and N-termini of the N- or O-glycosyl amino acid or peptide as well as of the glycan throughout the synthesis. Furthermore, protection of the C- and N-termini should both be of the temporary type, which can be removed under mild selective conditions to have the peptide elongated in either direction. 

The introduction of retro-, retro-inverso-, and PMRI-peptides with free and blocked C-and N-termini has been successful in numerous biological systems such as neurotransmitters, inhibitors of proteases and protein kinases, sweeteners, antimicrobial peptides, hormones, adhesion molecules, antigenic epitopes, immuno-modulators, and immunological probes. Table 1 provides an exhaustive list of retro-, retro-inverso-, PMRI-, and end-group-modified re/ro-mvmo-pseudopeptides derived from bioactive peptides. 

The third principle is that the side chain of Ala can hinder the solvation of NH and CO groups that need to make hydrogen bonds with solvent.35 This is important for the C- and N-termini of the helixes.36 There is an empirical correlation that relates A A GG]y AIa to both AAHP and the difference in solvent-accessible surface area of NH and CO groups in the helix that require solvation (AAHB, — area of Ala-containing helix — area of Gly-containing helix) ... 

Figure 9.14 Proteoglycan aggregate found in cartilage. C and N are C and N termini of the core protein. Long wavy lines represent chondroitin sulfate, whereas the short lines represent keratan sulfate. All are linkied to the core protein via the O-serine linkage, except for a few oligosaccharide chains near the N terminus of the core protein. LP is link protein, and HA is hyaluronic acid. (Reproduced by permission from Hascall V. Introduction. Functions of the Proteoglycans, Ciba Foundation Symposium 124. New York Wiley Sons, 1986, p. 2.)...

Fig. 6. The Flock House virus has an icosahedral symmetry with the y-peptide and the C and N termini of the /3-protein lying internally and away from the surface. However, time resolved proteolysis data indicates that the viral capsid is highly mobile and that internal domains are transiently exposed on the surface...

The arrangement of coordinating cysteine residues is highly conserved in all Rds including the Rd-type centers in nonheme peroxidases, and involves Cys-X2-Cys motifs near the C- and N-termini. Desulforedoxin and the Dx-type centers in 2Fe SORs provide an interesting variant with Cys-X2-Cys and Cys-Cys motifs for the coordinating cysteine residues the stereochemical constraint imposed by the adjacent cysteines... 

These derivatizations are highly selective, and may thus allow PSD measurements to be carried out on peptides after modification. Such a protocol would significantly enhance our ability to derive sequence information from PSD spectra, because the mass shifts observed in fragments help locate the particular residue within the peptide, and also confirm assignments of fragments as arising from N- or C-terminal regions. In addition to derivatizations that may modify the C- and N-termini and the derivatization of tyrosine residues, we have carried out oxidation of methionine residues with sufficient specificity to enable measurement of PSD spectra. 

Left schematic representation of the build-up of the chloroperoxidase from Cur. inaequalis. Helices are drawn as cylinders and /3-strands as broad arrows. The C and N termini are indicated.Reproduced from A. Messerschmidt and R. Wever, Proc. Natl. Acad. Sci. USA 93, 392-396. Copyright (1996), with permission from the National Academy of Sciences, USA. Right superposition of the active sites of the algal (A. nodosum) bromoperoxidase (dark) and the fungal Cur. inaequalis) chloroperoxidase (light).l l Reproduced from M. Weyand et al, J. Mol. Biol. 293, 595-611. Copyright (1999), with permission from Elsevier. 

In side-chain anchoring the amino acid side-chain is linked to the solid support and the C- and N-termini are orthogonally protected. Once chain elongation is finished, deprotection of both ends and subsequent cyclization and cleavage delivers the final cyclized product. Numerous amino acids have been used for side-chain anchoring, including Asx/Glx [155-161], Lys/Orn [158, 162], Ser/Thr [159, 163], Tyr [159, 163, 164], His [165, 166] and Cys [167, 168], on the usual supports and linkers for peptide synthesis (Figure 18.12). 

Prochloron spp. synthesize patellamides using a bacteriocin-like process. " The final patellamide structures are directly encoded on a precursor peptide, PatE. This linear, ribosomally encoded peptide must be modified and cleaved to yield heterocyclized, macrocyclized patellamides. In particular, the patellamides must be cut out of the precursor peptide from both their C- and N-termini, a property not yet observed in any other cyclic... 

Fig. 5 Crystal structure of papain [87], showing the catalytic triad composed of cysteine 25 (Cys), histidine 159 (His) und asparagine 175 (Asn) as well as the C-and N-termini...

Backbone amide linker (BAL), a linker moiety for an approach to solid-phase synthesis of C-terminal-modified and cyclic peptides. The growing peptide is anchored via a backbone nitrogen that allows considerable flexibility in management of the C- and N-termini. The tris(alkoxy)benzylamide-based handle/support has been success-fiilly used as BAL [K. J. Jensen et al., J. Am. Chem. Soc. 1998, 120, 5441],... 

SCHEME 9.5 Use of ring-closing and ring-opening metathesis as an aid to cyclization of a peptide at the C and N termini. 

C and N termini at a stage when the central region of the protein behaved as a random coil polymer. 

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