Overlapping peptide screening

Overlapping Peptide Screening. This method is based on a set of short overlapping synthetic peptides that span the entire sequence of the therapeutic protein of choice (Yeung et al., 2004). For example, in order to screen the variable region of both the heavy and light chain of a therapeutic IgG for potential T cell epitopes, at least different 15-mer peptides, overlapping by... 

For the cycloscan, conformational libraries are synthesized by cyclization of continuous or noncontinuous bioactive epitopes and not by their insertion into a scaffold. Originally, the concept of cycloscan was introduced for the generation of backbone-cyclized peptide libraries 467 however, cycloscan can also be applied to other modes of cyclization. In this approach all components of each sublibrary bear the identical sequence, and differ from each other in distinct parameters that affect their conformation, but do not alter their connectivity, and hence their potential bioactivity. This is achieved by gradually introducing discrete conformational perturbations, which allow an efficient screening of the conformational space of the parent peptide. The majority of the components of such libraries should be inactive, because they do not overlap the bioactive conformation. However, the peptide that does fit the bioactive conformation should be very potent and have all the pharmacological advantages of cyclic peptides. 

The electronic properties of amino acid side chains are summarized in Table 3, and they represent a wide spectrum of measures. The NMR data are derived experimentally (37). The dipole (38), C mull, inductive, field, and resonance effects were derived from QM calculations (15). The VHSE5 (39) and Z3 (25) scales were developed for use in quantitative structure-activity relationship analysis of the biologic activity of natural and synthetic peptides. Both were derived from principal components analysis of assorted physico-chemical properties, which included NMR chemical shift data, electron-ion interaction potentials, charges, and isoelectric points. Therefore, these scales are composites rather than primary measures of electronic effects. The validity of these measures is indicated by their lack of overlap with hydrophobicity and steric parameters and by their ability to predict biologic activity of synthetic peptide analogs (25, 39). Finally, coefficients of electrostatic screening by amino acid side chains (ylocal and Ynon-local) were derived from an empirical data set (40), and they represent a composite of electronic effects. 

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