We report the synthesis and characterization of a novel secondary structural motif, the poly-proline beta-turn helix. This motif is found in the proline-rich immunogenic domains of feline retroviruses, mucins and many proline-rich tandem repeat-containing surface proteins. We describe the synthetic methodology to directly synthesize natural and engineered immunogens of up to 100+ amino acids. Using manual solid-phase peptide synthesis modified for optimal efficiency, we directly synthesized 1, 2, 3, 4 and 5.25 tandem repeats corresponding to 20, 40, 60, 80, 105 amino acids of the human mucin muc-1, the complete 60 amino acid proline-rich neutralization domain of feline leukemia virus, and 70 and 72 amino acids of two very hydrophobic engineered tandem repeat proteins. High pressure liquid chromatography and mass spectrometry results indicate that the desired peptide can be synthesized up to 92% pure. The secondary structures of these peptides were studied using circular dichroism (CD) spectroscopy. The CD spectra revealed a characteristic intense negative band at 198 nm. A melting of structure could be demonstrated with increasing temperature as measured by decreasing molar ellipticity at 198 nm. The intensity of the molar ellipticity at 198 nm, as compared to the molar ellipticity of random coil, non-proline-containing peptides, led to the conclusion that the large, intense negative band at 198 nm is diagnostic of the poly-proline beta-turn helix.(ABSTRACT TRUNCATED AT 250 WORDS)