The stabilizing effects of hydrophobic cores on peptide folding of bovine‐pancreatic‐trypsin‐inhibitor folding‐intermediate model

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Abstract
A synthetic peptide model composed of α-helical and β-sheet portions (PαPβ) is a crucial folding intermediate in the folding of bovine pancreatic trypsin inhibitor (BPTI), which contains 30 amino acid residues, and provides a good model for studying the folding structure. Using this model the roles of hydrophobic cores, such as non-polar amino acids and a short β strand, in the folding structure stability were investigated by deleting the hydrophobic amino acids or substituting with Ala. As a first step, a mutant peptide, Pα6Pβ1, was made by removing the four residues (NNFK46) from the N-terminus of Pα which make a short β strand in native BPTI, and each of the hydrophobic cores, Phe45 of Pα and Tyr21 of Pβ, were substituted by Ala. Without the short β strand the peptide still folds in spite of its low solubility, suggesting that a simple α helix and central antiparallel β sheet contain sufficient information to direct the folding of this region of molecule. The peptide without Tyr21 was much more unstable than Pα6Pβ1, such that most of the folding structure collapsed even at 0°C, whereas without Phe45 the structure was more stable than Pα6Pβ1. This indicates that the hydrophobic interactions of Tyr21 in Pβ are more important in BPTI folding.