To compare the counteracting effects of methylamines trimethylamine N-oxide (TMAO) and betaine on the actions of urea, we have determined the apparent transfer free energies (Delta g(tr)') of zwitterionic glycine peptides: glycine (Gly), diglycine (Gly(2)), triglycine (Gly(3)), and tetraglycine (Gly(4)) from water to methylamine and urea, and also the blends of methylamine and urea at a 1:2 ratio as well as various urea concentrations (0.5-8M) in the presence of I M methylamine. The Delta G(tr)' values of the blends of methylamine with urea revealed that the methylamine strongly counteracted the urea actions on glycine peptides. However, the methylamine partially counteracted the deleterious effects of urea on the Gly(4) in the cases of higher urea concentrations (4-8 M) in the presence of I M methylamine. The experimental results were further used to estimate the transfer free energies (Delta g(tr)') of the peptide backbone unit (-CH2C=ONH-) contributions. (C) 2009 Elsevier B.V. All rights reserved.