Peptide analog, solution

The truncated peptide analogs were used to demonstrate the specificity of the method and to evaluate the limit of quantitation of potential impurities. Potential impurities were spiked into a solution of IB-367 at 0.05%, 0.1%, 0.2%, 0.5%, and 1% to assay the linearity of potential impurities at low concentrations. The method exhibited acceptable linearity for impurities from 0.05 to 1%. The relative response factors of these analogs were assessed to determine area normalization feasibility. 

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). 

Jorgensen, T.J.D. Roepstorff, P Heck, A.J.R. Direct Determination of Solution Binding Constants for Noncovalent Complexes Between Bacterial Cell Wall Peptide Analogs and Vancomycin Group Antibiotics by Electrospray Ionization Mass Spectrometry, AnaZ. Chem. IQ, 4427 432 (1998). 

The peptide analog of valinomycin, cyclo-(D-Val-L-Pro-L-Val-D-Pro)3 (= PV) forms more stable complexes with alkali metal cations than valinomycin (cf. Section 5.3). From NMR data, dissociation rate constants of 5 s 1 for the Li+ complex and < 1 s x for the Na+ and K+ complexes in solution have been estimated61). At lipid bilayers, a 104 times higher concentration of PV than of valinomycin is required to produce a comparable increase in K+ conductance282). It has been proposed that the dissociation of the complex could be the rate limiting factor of the ion transport by PV in bilayer membranes61). 

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... 

Lowik et demonstrated that the secondary structure of certain peptide sequences conjugated to single Ci8 alkyl chains at both the N- and C-termini could be induced upon incorporation into a liposome membrane. A sequence derived from the circumsporozoite (CS) protein of the malaria parasite Plasmodium falciparum was chosen, as within the natural protein the Asn-Pro-Asn-Ala repeat is known to adopt a j6-tum. Both the unmodified peptide in solution and the analogous peptide with only one alkyl chain showed random coil folding characteristics. However, when the double alkylated peptide was inserted into l,2-dimyristoyl-OT-glycero-3-phosphoethanol-amine (DSPC) liposomes the peptide folded into a P-hairpin. This simple approach is a convenient way for stabilizing a variety of peptides into their preferred secondary structure and might be employed in the presentation of multiple (hairpin) epitopes. 

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. ... 

Jorgensen, T. J. D. Roepstorff, P. Heck, A. J. R. Direct determination of solution binding constants for noncovalent complexes between bacterial cell wall peptide analogs and vancomycin group antibiotics by electrospray ionization mass spectrometry. Anal. Chem. 1998, 70(20), 4427-4432. 

A detailed investigation on the thermal denaturation of such a protein and of the thermodynamics of association of S -protein with -peptide and with synthetic S-peptide analogs seemed therefore particularly interesting. We decided to study the thermal denaturation of intact RNase-A by means of differential scanning calorimetry, which as far as I know, we were the first to apply to the study of concentrated biopolymers solutions [16] using a commercially available apparatus, and then to study with the LKB microcalorimeter the enthalpy of recombination of -protein with 5-peptide as well as with S-peptide analogs [7]... 

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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