Model peptide sequences

Oehlke and coworkers have described the cellular uptake properties of a simple a-hehcal amphipathic model peptide sequence (Lys-Leu-Ala-Leu-Lys-Leu-Ala-Leu-Lys-Ala-Leu-Lys-Ala-Ala-Leu-Lys-Leu-Ala) in the context of a drug delivery vehicle [72]. On the basis of the data presented, it was proposed that non-endocytosis mechanism(s) were involved in the uptake into mammalian cells. The similarity between our b2 aPNA-sequence to that of this amphipathic model peptide makes it tempting to suggest that a similar uptake mechanism is involved in the cellular uptake of aPNAs. Further experimentation is necessary to test this hypothesis. 

The experimental approaches employed for these purposes involve the chemical synthesis and conformational studies of model peptide sequences (homo- and co-oligopeptides) and polypeptides, semisynthesis of proteins and the comparison of their function with natural proteins, and structure-activity correlation studies using peptide analogs. The conformational preferences of the model peptides in solution are usually determined by various spectral measurements. The x-ray structure analysis, which is... 

Special phosphonium salts, such as (benzotriazol-l-yl-oxy-)tris(dimethylamino)-phosphonium and (benzotriazol-l-yl-oxy-)tris(pyrrolidino)phosphonium salts with hexafluorophosphate counter anion (Fig. 10) have been introduced as coupling reagents in the synthesis of four model peptide sequences. ... 

Table 2 shows a list of collagen model peptides which have teen prepared. Many efforts have been made to prevent racemization. The polycondensation reaction seemed to be more sensitive to racemization than the coupling steps preparing the monomeric tripeptide. Therefore, the sequence of the monomer was selected with Gly or Pro at the C-terminal chain end, because racemization is mostly favored at the carboxy-activated amino acid, and these amino acids cannot racemize. 

The model peptides should contain a well-defined sequence, should be pure and possess a uniform chain length. These are the prerequisites to the interpretation of the results of the thermodynamic measurements on the basis of the model concepts (e.g. AON model ). 

It is known that native collagen contains tripeptide sequences which, because of being homopolypeptides, are not able to give rise to triple-helical tertiary structures (e.g. Gly-Pro-Leu, Gly-Pro-Ser). The reason for this and for the above-mentioned low thermostability of the synthetic homopolypeptides is presumably to be found in the fact that in the case of the model peptides with their monotonously repeated tripeptide sequences, special interactions between the side chains of the different amino acid residues as postulated by Ward and Mason are no more possible157). 

Fig. 5. Comparison of ab initio, DFT/BPW91/6-31G -computed IR and VCD spectra over the amide I, II, and III regions for model peptides (of the generic sequence Ac-Alaw-NHCH3). These are designed to reproduce the major structural features of an o -helix (top left, n— 6, in which the center residue is fully H-bonded), a 3i helix (PLP Il-like, top right, n— 4), and an antiparallel /1-sheet (n= 2, 3 strands, central residue fully H-bonded) in planar (bottom left) and twisted (bottom right) conformations. The computations also encompass all the other vibrations in these molecules, but those from the CH3 side chains were shifted by H/D exchange (CH3) to reduce interference with the amide modes.

Fig. 1 Solid-state NMR structure analysis relies on the 19F-labelled peptides being uniformly embedded in a macroscopically oriented membrane sample, (a) The angle (0) of the 19F-labelled group (e.g. a CF3-moiety) on the peptide backbone (shown here as a cylinder) relative to the static magnetic field is directly reflected in the NMR parameter measured (e.g. DD, see Fig. 2c). (b) The value of the experimental NMR parameter varies along the peptide sequence with a periodicity that is characteristic for distinct peptide conformations, (c) From such wave plot the alignment of the peptide with respect to the lipid bilayer normal (n) can then be evaluated in terms of its tilt angle (x) and azimuthal rotation (p). Whole-body wobbling can be described by an order parameter, S rtlo. (d) The combined data from several individual 19F-labelled peptide analogues thus yields a 3D structural model of the peptide and how it is oriented in the lipid bilayer...

A. Frank and P. Pevzner. PepNovo De novo Peptide Sequencing via Probabilistic Network Modeling. Anal. Chem., 77, no. 4 (2005) 964-973. 

Crystallization is the basis of silk strength. But if crystallization were excessive, then the silk would become very brittle rather than being the flexible fiber that it is. The study of model peptides inspired from silk sequences has shown catastrophic and uncontrollable aggregation suggesting... 

A series of short peptide fragments of type III collagen have been used to find binding sites with other molecules. DDR-2 has been shown to interact with a type III collagen model peptide with the minimal sequence of GVMGFO (where O is 4-hydroxyproline)." It is interesting to note that this same sequence is also involved with the collagen interaction of SPARC." ... 

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