A-helix conformation

Robust peptide-derived approaches aim to identify a small drug-like molecule to mimic the peptide interactions. The primary peptide molecule is considered in these approaches as a tool compound to demonstrate that small molecules can compete with a given interaction. A variety of chemical, 3D structural and molecular modeling approaches are used to validate the essential 3D pharmacophore model which in turn is the basis for the design of the mimics. The chemical approaches include in addition to N- and C-terminal truncations a variety of positional scanning methods. Using alanine scans one can identify the key pharmacophore points D-amino-acid or proline scans allow stabilization of (i-turn structures cyclic scans bias the peptide or portions of the peptide in a particular conformation (a-helix, (i-turn and so on) other scans, like N-methyl-amino-acid scans and amide-bond-replacement (depsi-peptides) scans aim to improve the ADME properties." ... 

In Section 7.7.3.3, methods for quantitating a-helix and other secondary structural types in peptides were described. These are generally applicable to a series of peptides in which a regular conformation [a-helix, (3-sheet, poly(Pro)II] is in equilibrium with an ensemble of unordered conformations, as evidenced by an isodichroic point observed over a range of temperature, pH, or solvent composition. 

According to whether we proceed upwards or downwards when passing from the third to the fourth atom in the middle plane, we have the beginning of a right- or a left-handed helix. Sulfur chains, and, of course also all the many sulfanes and sulfane-derivatives, i.e., compounds containing chains of sulfur atoms, thus must have helical conformations. A helix with zero translation leads to a non-planar ring. 

From the H CRAMPS NMR spectra, therefore, it was possible to determine the NH proton chemical shift value for [Ala ]n-2 (a-helix 6 = 8.0) which is identical with that determined using BR-24 (2.0 kHz). Further, it was possible to determine the " NH proton chemical shift for [Ala ]n-1 (/3-sheet, 6 = 8.6) using the MREV-8 pulse sequence at 3.5 kHz. However, unfortunately, the NH proton chemical shift values for [Ala]n-2 and [Ala]n-t could not be determined because the line shapes of the " NH signals exhibit an asymmetric doublet pattern in this system also. Thus, it is found that determination of the true NH chemical shift of poly(L-alanines) can be achieved to measure fully N-labelled samples at higher MAS speed (3.5 kHz) and that these chemical shifts depend on conformation (a-helix 6 = 8.0 /3-sheet S = 8.6). This is the first determination of the true NH proton chemical shifts of poly(L-alanines) by H CRAMPS NMR. 

Table 2. Isotropic 15N chemical shifts of some homopolypeptides with various conformations (a-helix, /3-sheet, aL-helix, wL-helix, PGI, PGII, PPI and PPII forms) in the solid state (ppm from 15NH4N03, 0.5ppm).

To summarize, the complex formation between cationic polypeptides and anionic surfactants is initiated through coulombic interaction and followed by a cooperative binding of successive surfactant ions. The nonpolar tails of clustered surfactant molecules can provide a hydrophobic environment that stabilizes an ordered conformation — a helix or a 8-form, which depends not only on the number of methylene groups of lysine and its homologs but also on the chain length of the surfactants. Excess surfactant molecules may cluster onto the bound surfactant ions in a "double layer" fashion with their polar heads exposed to the aqueous medium and nonpolar tails shielded from the polar environment. For the 8-pleated sheets a bilayer can also be formed between bound surfactant molecules which are sandwiched between two polypeptide chains. 

The above conaderations ate described in fiiller detail in previous papers [6,7] and indicate that macromolecules assuming a single chirality conformation can show chiroptical properties characteristic of the conformation itself. Moreover, if chromophores are present in the side chains specific chiroptical properties can arise from dipole-dipole dectronic interactions among these chromophores disposed along the chirally arranged backbone. This situation is cleariy shown in poly-a-amino adds, in which spedfic and typical chiroptical properties are assodated with spedfic and typcal conformations (a-helix, -structures, random coil) [8]. 

The spectra and the relative ratio of the secondary conformations (a-helix and (3-sheet) of prion infected brains in frozen sectioned tissue were measured by Fourier-transform infrared (FT-IR) microscopy. The tissues were obtained from the Prion Diseases Research Center in the National Animal Health Institute (PDRC/NAHI) of Japan. Both prion infected and normal brain tissues of mice and hamster were embedded adjacently and were frozen-sectioned for the FT-IR microscopy. Spectra from the normal and the prion-infected brain tissue sides were compared. The C-H stretching components in the normal tissue and the amide-I, -II components in the prion tissue were larger than the other sides, respectively. Furthermore, we developed the software to analyze the relative ratios of protein secondary conformation in the tissue by FT-IR microscopy. Results showed that the relative ratio of the p-sheet component was at a higher level (37-40%) in the prion side compared to that in the normal... 

Figure 1 The circular dichroism of polypeptides with different conformations. (—) a-helix, poly-L-lysine in water, pH 11.1,22°C ( ) /S-sheet, poly(Lys-Leu-Lys-Leu) in 0.5 M NaF at pH 7 ...

Proteins. Quantitation of polypeptide conformation, a-helix, /3-sheet, /3-turns, etc. characterization of cysteine-SH side chains conformation of disulfide -S-S-linkages strength of hydrogen bonds to tyrosine-OH exposure to hydrophobic/hydrophilic environments of tryptophan side chains... 

Costa et al. [18] employed ATR-FTIR spectroscopy to analyze the interactions between biopolymers and P(NiPAM-co-MAA) MGs (Figure 6.10). The spectra are difficult to analyze since the characteristic PE bands overlap with the amide vibrations. Moreover, the exact band positions for the polypeptides depend on their conformation (a-helix, p-sheet, or random coil), due to vibrational interactions between the peptide groups and the... 

Conformational free energy simulations are being widely used in modeling of complex molecular systems [1]. Recent examples of applications include study of torsions in n-butane [2] and peptide sidechains [3, 4], as well as aggregation of methane [5] and a helix bundle protein in water [6]. Calculating free energy differences between molecular states is valuable because they are observable thermodynamic quantities, related to equilibrium constants and... 

Zhang L and J Hermans 1994. 3io-Helix versus a-Helix A Molecular Dynamics Studv of Conformational Preferences of Aib and Alanine. Journal of the American Chemical Society 116 11915-11921. 

The primary structure of a peptide is its ammo acid sequence We also speak of the secondary structure of a peptide that is the conformational relationship of nearest neighbor ammo acids with respect to each other On the basis of X ray crystallographic studies and careful examination of molecular models Linus Pauling and Robert B Corey of the California Institute of Technology showed that certain peptide conformations were more stable than others Two arrangements the a helix and the (5 sheet, stand out as... 

Secondary structure (Section 27 19) The conformation with respect to nearest neighbor ammo acids m a peptide or pro tern The a helix and the pleated 3 sheet are examples of protein secondary structures... 

Figure 1.10 Helical conformations in polymer molecules, (a) A vinyl polymer with R substituents has three repeat units per turn, (b) The a helix of the protein molecule is stabilized by hydrogen bonding. [From R. B. Corey and L. Pauling,/ end. Inst. Lombardo Sci. 89 10 (1955).]...

Fig. 2. Protein secondary stmcture (a) the right-handed a-helix, stabilized by intrasegmental hydrogen-bonding between the backbone CO of residue i and the NH of residue t + 4 along the polypeptide chain. Each turn of the helix requires 3.6 residues. Translation along the hehcal axis is 0.15 nm per residue, or 0.54 nm per turn and (b) the -pleated sheet where the polypeptide is in an extended conformation and backbone hydrogen-bonding occurs between residues on adjacent strands. Here, the backbone CO and NH atoms are in the plane of the page and the amino acid side chains extend from C ...

Figure 6.21 Schematic diagram of the conformational changes of calmodulin upon peptide binding, (a) In the free form the calmodulin molecule is dumhhell-shaped comprising two domains (red and green), each having two EF hands with bound calcium (yellow), (b) In the form with bound peptides (blue) the a helix linker has been broken, the two ends of the molecule are close together and they form a compact globular complex. The internal structure of each domain is essentially unchanged. The hound peptide binds as an a helix.

The GAL4 recognition module therefore contains only one protein side chain, Lys 18, that provides specific interactions with the DNA. The remaining specific interactions with DNA are from main-chain atoms and depend critically on the correct conformation of the protein. The correct positioning of the C-terminus of the a helix is particularly important for recognition. This is to date the only example of a protein-DNA interaction in which... 

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