Peptide analog, solution conformation

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... 

Solution Conformation. Knowledge of solution conformation of constrained peptide analogs has proven very useful for corre-... 

Cyclic peptides are of interest as turn mimetics or as conformationally constrained peptide analogs. The cyclization of peptides can either be performed after cleavage from the support in solution (see, e.g. [58]) or while still on the support. Besides cycli-zations of the peptide backbone, peptides can be cyclized through their side chains or by means of a non-natural spacer. To cyclize the backbone of a peptide on an insoluble support, the peptide must be attached to the support either by a backbone amide linker [59] or via the side chain of an amino acid [60] (Figure 16.7). 

A common problem is the identification of molecular conformations that satisfy NMR constraints. Sanderson et al. describe the use of a GA to determine possible solution conformations of a cyclic Arg-Gly-Asp peptide analog that were consistent with NMR data. Torsions were encoded as binary numbers. In order to perform full cyclic conformational search the macrocycle was broken and constraints were applied to ensure ring closure. Beckers et al. describe a distributed GA that is used to obtain biopolymer conformations consistent with NMR data. ... 

These y9 -peptides are not expected to adopt a 3i4-helical conformation in an aqueous environment because of the destabihzing effect of cationic charges. The circular dichroism spectrum of a non-labeled analog of 165 does not display the characteristic signature of the 3i4-helix in aqueous solution however it is highly hehcoidal in MeOH. 

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