Infrared frequency region of 2000-2600 cm(-1) (i.e., ca. 4-5 mu m in wavelength) is a well-known open spectral window for peptides and proteins. In this work, six unnatural amino acids (unAAs) were designed to have characteristic absorption bands located in this region. Key chemical groups that served as side chains in these unAAs are C C, Phe-C C, N=C=O, N=C=S, P-H, and Si-H, respectively. Cysteine (a natural AA having S-H in side chain) was also studied for comparison. The anharmonic vibrational properties, including frequencies, anharmonicities, and intermode couplings, were examined using the density functional theory. Broadband linear infrared (IR) and two-dimensional (2D) IR spectra were simulated for each molecule. It is found that all of the side chain modes have significant overtone diagonal anharmonicities. All have moderate transition dipole strengths except the C C and S-H stretching modes, in comparison with the C=O stretching mode. In each case, a collection of 2D IR cross peaks were predicted to appear due to the presence of the side chain groups, whose strengths are closely related to the intramolecular anharmonic interactions, and to the transition dipole strengths of the coupled vibrators. Further, potential energy distribution analysis and high-order anharmonic constant computation showed that these IR probes possess a varying degree of mode localization. The results suggest that these IR probes are potentially useful in complementing the well-studied amide-I mode, to investigate structures and dynamics of peptides and proteins.