Capping peptides

Fig. 11. Purification scheme for full-length glycolate-capped peptides using a reversible biotin capping agent...

Figure 31. N-cap and C-cap templates and the corresponding conformationally constrained N- and C-capped peptides.

The conformational properties of peptides linked to these capping templates were investigated by CD spectroscopy, NMR-measurements, and X-ray diffraction analysis.204 Figure 32 shows the CD spectra of the two template-linked model peptides 102,103, and an uncapped 12-mer reference peptide 104 with comparable amino acid sequence (Boc-Ala Aib-Alag-Aib-Alaj-pIa). The CD spectra exhibit the negative maxima at about 207 and 222 nm, characteristic for a-helical peptides. Based on the ellipticity values at 222 nm (amide n — 7t transition) the N-capped peptide was calculated to be approximately 90% a-helical, whereas the helicity of the reference peptide is approximately 50% in TFE/H20 (1 1). 

The basic steps of tffis strategy are shown in Scheme 1. It should be emphasized that impurities generated by side reactions occurring either during synthesis or during deprotection and that affect both the target sequence and capped peptides are not removed by this technique. 

This is demonstrated here with DFT-MD simulations to extract the vibrational spectrum of the Ac-Phe-Ala-NH2 peptide (capped peptide composed of phenyl and alanine residues, labeled FA in the remainder of the text see Fig. 9) in the far-IR domain, in relation to IR-UV ion-dip experiments [111]. With dynamical spectroscopy, one has to keep in mind that the length of the trajectories has to be commensurate with the domain investigated. Hence, to sample the vibrational modes and then-couplings in the 100-1,000 cm region, we have accumulated trajectories of 30 ps and make an average for the final theoretical specfrum over two ttajectories (i.e., 60 ps sampling in total). 

Fig. 4 Secondary structure gallery, from gas phase IRAJV laser spectroscopy of a series of modei capped peptides p-strand [135], y-tum (in combinatirai with a nearby p-strand N-terminai [84, 94]), 2y ribbon [82], p-tum [81], incipient Sjo helix [85], p-hairpin [107] and antiparallel P-sheet model [124]. Spectra of Ac-(Ala)2-0-Bn and the Ac-Val-(Me)Tyr-NH-Me dimer are adapted from [135] and [124] respectively, with the permission of ACS. Spectrum of Ac-(Ala)3-Phe-NH2 is adapted from [107] with the permission of Wiley...

Fig. 5 Gallery of NH-)t interactions between an aromatic residne (Phe, Tyr or Tip) and a backbone amide NH bond, from gas phase IR/UV laser spectroscopy of a series of model capped peptides a folded backbone (y-tum), without and with a NH-ic interaction within the Phe residue [70], an extended backbone on Phe, with the interaction of Phe with NH of the next residue [84, 94]) and various aryl-rich dipeptides, leading to sandwich-Uke conformations of the NH embedded in the aryl environment and to significantly red shifted IR NH stretch signatures [112]. In the latter cases, the simultaneous presence of two it H-txaids raiginating from the same NH moiety (made possible through a direct interactiim between aromatic side chains) is indicated by the 3D-NCI plot of these interactions [193, 194]...

As mentioned above, toluene and cresol can be considered as poor man s models for the interaction between the aromatic side-chain residues of phenylalanine (Phe) and tyrosine (Tyr). To get a little closer to reality and to introduce possible interactions with a peptide chain model, subsequent investigations were extended to include complexes formed between monosaccharides such as Glc and Gal, and the capped peptides, AcPheNHMe [48,49] and AcTyrNHMe [59] see Fig. 19. 

Jones, J. W. Sasaki, T. Goodlett, D. R. Turecek, F. Electron capture in spin-trap capped peptides. An experimental example of ergodic dissociation in peptide cation-radicals. J. Am. Soc. Mass Spectrom. 2007, 18, 432-444. 

Harper, E., and Rose, G. D., 1993. Helix stop signals in proteins and peptides The capping box. Biochemistry 32 7605-7609. 

Fig. 11 Experimental set-up for small-scale microwave SPPS of /S-peptides (SPE = solid-phase extraction). 1 Pasteur pipet for N2 agitation 2 10 mL glass vial 3 4mL solid-phase extraction tube 4 DMF 5 coupling solution 6 resin 7 polyethylene frit 8 Luer-lock cap...

Inspired by the elastin-based side-chain polymers, Lemieux et al. prepared elastin-based stimulus-responsive gold nanoparticles. To this end, they capped gold particles with a layer of a single repeat of thiol-functionalized VPGVG peptides (Fig. 17a). These nanoparticles showed LCST behavior, which was modulated by varying the pH of the solution [131]. 

Figure 38-7. Activation of elF-4E by insulin and formation of the cap binding elF-4F complex. The 4F-cap mRNA complex is depicted as in Figure 38-6. The 4F complex consists of elF-4E (4E), elF-4A, and elF-4G. 4E is inactive when bound by one ofa family of binding proteins (4E-BPs). Insulin and mitogenic factors (eg, IGF-1, PDGF, interleukin-2, and angiotensin II) activate a serine protein kinase in the mTOR pathway, and this results in the phosphorylation of 4E-BP. Phosphorylated 4E-BP dissociates from 4E, and the latter is then able to form the 4F complex and bind to the mRNA cap. These growth peptides also phosphorylate 4E itself by activating a component of the MAP kinase pathway. Phosphorylated 4E binds much more avidly to the cap than does nonphosphorylated 4E.

A-Acetylimidazole was found to be a very efficient terminating (capping) agent in the solid-phase synthesis of peptides.t40],[41] A terminating agent is used to block any N-terminal amino groups that have not reacted in the coupling steps.[40]... 

Thomas, S. T., Loladze, V. V., and Makhatadze, G. I. (2001). Hydration of the peptide backbone largely defines the thermodynamic propensity scale of residues at the i position of the c-capping box of a helices. Proc. Natl. Acad. Sci. USA 98, 10670-10675. 

Fig. 19 Structure of LA-PRX (above) and degradation of LA-PRX (below), (a) Threaded a-CDs prevent hydrolysis of PLLA in LA-PRX. (b) LA-PRX converts into LA-pPRX by peptide linkage cleavage at bulky end-capping groups through action of papain, (c) Ester bond hydrolysis in the PLLA chain begins by an exposure of PLLA to water by release of a-CDs from LA-pPRX. Reprinted from [292] with permission...

Nanoparticle surface modification is of tremendous importance to prevent nanoparticle aggregation prior to injection, decrease the toxicity, and increase the solubility and the biocompatibility in a living system [20]. Imaging studies in mice clearly show that QD surface coatings alter the disposition and pharmacokinetic properties of the nanoparticles. The key factors in surface modifications include the use of proper solvents and chemicals or biomolecules used for the attachment of the drug, targeting ligands, proteins, peptides, nucleic acids etc. for their site-specific biomedical applications. The functionalized or capped nanoparticles should be preferably dispersible in aqueous media. 

Poisoning and sometimes death from eating (unidentified) mushrooms is well known. In particular, Amanita sp. are particularly dangerous, with much emphasis on the death cap fungus , Amanita phalloides.24 The best known toxins are the amatoxins and phallotoxins, which are complex, bicyclic peptides. An unusual feature relates to sulfur a tryptophan (or substituted tryptophan) unit is linked to a cysteine sulfur at the carbon atom next to the NH group of the pyrrole ring, forming the unit, -CH2-S-C(NH)=C, e.g. in... 

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