We have designed a series of C-capping auxiliaries with various chain lengths based on alkyldiamines and monoguanylated diamines. These capping groups were incorporated synthetically at the C-terminus of a derivative of a poly-Ala helix. The free energy of interaction of the capping moiety (Delta Delta G(c) degrees) with the C-terminus of the helix was assessed by circular dichroism and calculated using a modified Lifson-Roig formalism described by Doig and Baldwin (Doig, A. J.; Baldwin, R. L. Protein Sci. 1995, 4, 1325) as well as AGADIR2s, an algorithm based on helix-coil transition theory developed by Munoz and Serrano (Munoz, V.; Serrano, L. Biopolymers 1997, 41, 495-509). The alkyldiamine auxiliaries serve as modest helix stabilizers with Delta Delta G(c) degrees, = -0.2 to -0.5 kcal mol(-1). The incorporation of monoguanylated diamines at the C-terminus leads to a further increase in cr-helicity resulting in Delta Delta G(c) degrees = -0.3 to -0.7 kcal mol(-1). Furthermore, a D-Arg carboxamide auxiliary is demonstrated to be an efficient C-capping residue with Delta Delta G(c) degrees = -1.2 kcal mol(-1). At high concentrations of NaCl (2 M), the capping effect is only partially screened, suggesting that this auxiliary imparts stabilization via charge/dipole interactions as well as through the formation of specific H-bonds between the auxiliary and C-terminal main chain carbonyls.