Algorithms for the quantitative validation of chiral properties of peptides

Abstract

Complexation with Cu(II) ion in strong aqueous base, combined with visible range circular dichroism detection, were used to quantitatively differentiate among the L‐enantiomers of the GG, GA, GY, AG, AA, AY, YG, YA, and YY dipeptides and the D‐enantiomer of GA. Using ellipticity data at all (n = 1500) wavelengths in the measured spectra, and two novel data reduction procedures, quantitative determinations were made of the compositions of binary mixtures. For mixtures made with the L‐GA and D‐GA enantiomers, the accuracy of the measured enantiomeric purities was better than 0.17 % over the 1–48 % range for the minor component. The method has considerable potential for use in quality control of peptide and protein biotechnological drug forms. Chirality 11:546–553, 1999. © 1999 Wiley‐Liss, Inc.

A convenient assay method for the quality control of peptides and proteins

“…1,2 Spectra for Cu(II)-D-histidine and Cu(II)-(D-histidinepeptide) mixed complexes were the focus for di-and tripeptide ligands. 3,7 Evidence was provided that confirmed that the stoichiometries and the complex formation con- stants were similar in magnitude within each series.…”

“…The 2-D model is effective in determining EP's with an accuracy unsurpassed by any other procedure. 1 The 3-D model, in contrast, is better suited for enantiomeric identification, and chemical purity determinations. 2,3 Only the former is considered in the context of this article.…”

Tripeptide discriminations using circular dichroism detection

“…The same objectives were achieved when the 3-D algorithm was applied to a series of dipeptides all of which had just one chiral center. 11 In the 2-D presentations of Figures 2, 3, 5, and 6, wavelength is an implied variable. For the evolution of the 3-D algorithm, wavelength is the third dimension.…”

“…The experimental procedure is a combination of the methods that were used to discriminate among related dipeptides 11 and insulins 12 and to measure EP's for glycyl-L-alanine and ephedrine mixtures. [9][10][11] Data reduction and spectral differentiations are done using variations on standardized mathematical algorithms and principal component analysis (PCA).…”

“…[9][10][11] Data reduction and spectral differentiations are done using variations on standardized mathematical algorithms and principal component analysis (PCA).…”