ABSTRACT:The adequacy of the hypothesis that the protected peptide solubility only weakly depended on their amino acid sequence was confirmed by the evaluation of the /J-sheet-structure stability of protected peptides. As the {J-sheet-structure stability of protected peptides is related with their solubility, it is investigated by the solvent-titration method using the protected host-guest peptides, Boc-(X-Glu(OBzl)-Ala-Leu-Gly)n-OPac (n= 1, 2) which have the same amino acid composition with Boc-(X-Ala-Glu(OBzl)-Leu-Gly).-OPac (n= I, 2) studied previously. In fact, the results show concurrently that the {J-sheet-structure stability of pentapeptides is useful for the estimation of protected peptide solubility in organic solvents and only weakly dependent on their amino acid sequence. It is also little weakly dependent on the solvation mechanism, by which peptides they solvate with an electron acceptor or donor solvent. The {J-sheet-structure stability of protected decapeptides is also strongly dependent on their amino acid composition and only weakly dependent on their amino acid sequence. The significance of the hypothesis for the prediction of the protected protein solubility is briefly discussed.