P-sheet conformations

Alternative approaches to imprint peptides via strong monomer template association have recently been reported, although no results of the chromatographic application of these phases have been shown. Strong complexation inducing a p-sheet conformation was possible using a designed functional monomer (21) [71]. Peptides... 

Figure 1.14 Secondary structure within proteins may be stabilized through hydrogen bonding between adjacent 7-chains, forming p-sheet conformations.

After a-helices, P-sheets are the most prominent secondary structure feature in globular proteins. However, the most widely used tool for secondary analysis, ultraviolet ECD, is so dominated by its sensitivity to the a-helix that, at best, it can only poorly characterize ( -sheet content. IR on the other hand has a good differential sensitivity to the p-sheet because of the large frequency shift ( 30 cm-1) from the helical band and because the extinction coefficient for model extended sheets is often higher than for other conformations. However, study of the p-sheet conformation with peptide models has long been hindered by their natural tendency to aggregate. Furthermore, no (or very few) peptide models of parallel sheets are available, to our knowledge. 

The abnormal deposits found in the brains of CJD victims consist of an abnormal isoform of PrP. Prion protein is normally found in cells. Detailed structural studies show that normal cellular PrP (PrP ) is a soluble protein whose conformation is rich in a-helices with very little P-sheet. The PrP protein extracted from the brains of CJD victims (i.e., PrP ) is identical in primary amino acid sequence to the normal PrP (PrP ). However, PrP has a much greater content of P-sheet conformation with little a-helical structure. Thus PrP is neurotoxic because of its three-dimensional structure. When the prion protein is predominantly in an a-helical conformation it is nontoxic when the prion protein is predominantly in a P-sheet conformation, it kills neurons. The prion protein is thus made neurotoxic not by its amino acid composition but by its conformation. This concept is both fascinating and terrifying. Prion diseases are transmissible thus prions are infectious agents. However, prions are not like bacteria or viruses, or other infectious microbes—they are simply protein molecules. Prions are not microbes with cell membranes and nucleic acids they are not living things. Indeed, prions are not even infectious molecules, they are infectious molecular shapes. 

In order to clarify the relationship between cross peaks and carbon proton inter-atomic distances, molecular model for the anti-parallel p-sheet conformation of PG and PLV have been calculated using reference data (Wiithrich, et al.)117 by the X-PLOR 3.1 program, and we measured the carbon-proton distances from the modeled structure (Table 14). The distances between the carbons and their directly bonded protons are ca. 1.1 A and their signals can be observed in the FSLG C H HETCOR spectrum with contact time of 0.2 ms. Further, in the FSLG C H HETCOR spectrum with a contact time of 0.5 ms the signals corresponding... 

Shibata, A., Yamamoto, M., Yamashita, T., Chiou, J.S., Kamaya, H., Ueda, I. (1992). Biphasic effects of alcohols on the phase transition of poly(ot-lysine) between Ot-helix and P-sheet conformations. Biochemistry, 31, 5728-5733. 

Figure 2. Far UV CD spectra of homopolymers which adopt a p-sheet conformation poly(Lys), pH 11.1 after heating, — poly(Lys), in 1% sodium dodecyl sulfate, — poly(Lys-Leu) in 0.1 M NaF, pH 7, . (From ref. 14)...

Figure 20. CP/MAS NMR spectra (a) and the expanded NMR spectra of the methyl alanine region (b) of SF matrices. The dotted arrow indicates the chemical shift of alanine in the p-sheet conformation[75].

Figure 22-6. The hydrogen bond association of the L-diamide phase in its antiparaUel P-sheet conformation with (A) N-TFA-L-a-amino acid alkyl ester and (B) A-TFA-d-a-amino acid alkyl ester. (Reprinted from reference 35, with permission.)...

Figure 22-7. Hydrogen bond association of A -acetyl-L-valyl-tertbutylamide phase in its parallel P-sheet conformation with the Al-TFA-a-amino acid isopropyl ester. (Reprinted from reference 36, with permission.)...

Studies on host-guest peptides have shown that incorporation of a proline residue into peptides which have a high tendency to fold into ordered secondary structures disrupts the onset of helical as well as P-sheet conformations and increases solubility and coupling rates.f Based on this observation, serine- and threonine-derived oxazolidine, and cysteine-derived thiazolidine derivatives (pseudoprolines) were proposed as valuable tools for combining protection of their side-chain functions with the simultaneous solubilization of the peptide chain. Due to the induction of kink conformations in the peptide backbone, originating from the preference of these pseudoproline residues to adopt the cis-imide bond configuration, insertion of such derivatives into peptides prevents self-association and P-structure formation. 

The cornified cell envelope is the outermost layer of a corneocyte, and mainly consists of tightly bundled keratin filaments aligned parallel to the main face of the corneocyte. The envelope consists of both protein and lipid components in that the lipid is attached covalently to the protein envelope. The envelope lies adjacent to the interior surface of the plasma membrane. " The corneocyte protein envelope appears to play an important role in the structural assembly of the intercellular lipid lamellae of the stratum corneum. The corneocyte possesses a chemically bound lipid envelope comprised of A-co-hydroxyceramides, which are ester linked to the numerous glutamate side chains provided possibly by both the ot-helical conformation and p-sheet conformation of involucrin in the envelope protein matrix. In the absence of A-oo-hydro-xyceramides, the stratum corneum intercellular lipid lamellae were abnormal and permeability barrier function was disrupted. 

Several cyclic peptides have between two and eight cysteine residues. They adopt a triple-stranded 3-sheet structure e.g. vertebrate defensins) or a P-hairpin-like structure (e.g thanatin, androctonin, gomesin, and tachyplesin from arthropods and protegrin from vertebrate) or a mixed a-helix/p-sheet conformation (e.g. invertebrate and plant defensins, including some vertebrate defensins). Several reviews have been published in the past years discussing the structure and the mode of action of cyclic AMPs from animals. The reader is referred to the reviews written by Powers and Hancock [108], Bulet et al. [4], Ganz [8], and Yount [88]. In this chapter, only cyclic peptides with a P-hairpin-like structure will be discussed. 

A single P-strand mimic was introduced by Hirschmann, Smith, and their coworkers based on the nitrogen-displaced and carbonyl-displaced pyrrolinone scaffolds (Fig. 14), which mimics both the hydrogen-bonding pattern and the side-chain orientation of the p-strand/p-sheet conformation of peptides (204). 

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