We investigated the change in the conformation Of poly(L-glutamic acid) from a random coil to an (x-helix in solutions of guanidinium salts with a dodecanoylamidoalkyl group, C(12)A(m)G (m = 0, 2, 3, 4, 6), where A. indicates a methylene spacer between the dodecanoyl group and guanidine and m is the number of methylene carbons. C(12)A(m)Gs (m = 0, 2, 3, 4) induced an alpha-helix in P(Glu), but C(12)A(6)G failed. Binding isotherms were constructed from the potentiometry of bound C(12)A(m)G and cooperative binding was observed, as found in many regular surfactants. All C(12)A(m)G gave a similar cooperative parameter and overall binding constants of comparative order (113 x 10(3) to 255 x 10(3)). In contrast to the methylene group in regular surfactants, the methylene spacer in C(12)A(m)G had a minor effect on hydrophobic interactions. C(12)A(0)G showed the strongest cooperative binding and effect on the formation of the alpha-helix in P(Glu). The methylene spacer interfered with C(12)A(m)G binding and alpha-helix formation in P(Glu).