A new algorithm, called convex constraint analysis, has been developed to deduce the chiral contribution of the common secondary structures directly from experimental CD curves of a large number of proteins. The analysis is based on CD data reported by Yang, J.T., Wu, C.-S.C. and Martinez, H.M. [Methods Enzymol., 130, 208-269 (1986)]. Application of the decomposition algorithm for simulated protein data sets resulted in component spectra [B (lambda, i)] identical to the originals and weights [C (i, k)] with excellent Pearson correlation coefficients (R) [Chang, C.T., Wu, C.-S.C. and Yang, J.T. (1978) Anal. Biochem., 91, 12-31]. Test runs were performed on sets of simulated protein spectra created by the Monte Carlo technique using poly-L-lysine-based pure component spectra. The significant correlational coefficients (R greater than 0.9) demonstrated the high power of the algorithm. The algorithm, applied to globular protein data, independent of X-ray data, revealed that the CD spectrum of a given protein is composed of at least four independent sources of chirality. Three of the computed component curves show remarkable resemblance to the CD spectra of known protein secondary structures. This approach yields a significant improvement in secondary structural evaluations when compared with previous methods, as compared with X-ray data, and yields a realistic set of pure component spectra. The new method is a useful tool not only in analyzing CD spectra of globular proteins but also has the potential for the analysis of integral membrane proteins.

The sequence Lys-Ser-Pro-Val-Pro-Lys-SerPro-Val-Glu-Glu-Lys-Gly repeats six times serially in the human midsized neuroframent (NF) protein (NF-M). To establish whether Lys-Ser-Pro-Val(Ala) is the major site for in vivo NF phosphorylation, peptides based on the human NF-M repeat were synthesized and chemically phosphorylated. These synthetic peptides were probed with 515 monoclonal antibodies (mAbs) that were raised to, and distinguished, several differentially phosphorylated forms of NF proteins. Studies with 95 of those mAbs that recognized the peptides before and after chemical phosphorylation demonstrated that a highly immunogenic epitope shared by the peptides is present in NFs from all species tested, including invertebrates. This suggests the phylogenetic conservation of a major NF phosphorylation site. Lastly, a cross-reactive antigenic determinant shared by the peptides and the major NF phosphorylation site was shown to exist in neurofibrillary tangles of patients with Alzheimer disease as well as in two neuron-specific microtubule-associated proteins (MAPs-i.e., MAP2 and tau.

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Rational control over helix and strand secondary structures is possible when conformationally restricted cyclic β‐amino acid residues are incorporated in the β‐peptides. Inversion of the relative configuration of these residues enables the preferred periodic structure to be switched from a helix to a single nonpolar strand (see picture).