Peptides are poor candidates for skin permeation. KTTKS is not an exception and cannot permeate skin in therapeutic amounts. However, chemical modification could be a good approach to overcome this problem. In our study, we used citronellic acid and perillic acid terpenes to synthesize Cit-KTTKS and Per-KTTKS, and KTTKS and Pal-KTTKS for comparison. We studied the aqueous stabilities of the compounds. Peptides permeations through a membrane model of n-hexadecane and human epidermis permeations of KTTKS, Pal-KTTKS, and Cit-KTTKS were determined. The results revealed that the aqueous solution of compounds remained stable at 32°C for 48 h. The membrane model permeation studies showed that KTTKS and Per- KTTKS were not detected in receptor phases, but Pal-KTTKS and Cit-KTTKS passed across the membrane model and showed estimated kp of 17×10–4 cm/h and 2.9×10–4 cm/h, respectively. The epidermis studies showed that KTTKS and Pal-KTTKS did not pass across the epidermis in detectable amounts, whereas Cit- KTTKS permeated epidermis with kp of 7.3×10–4 cm/h. The donor phase assay and mass-balance studies showed that Pal-KTTKS was trapped by about 48% in the epidermis and 20% in the model membrane. Based on these results, terpenes appear to be good candidates for peptide conjugation to increase the skin permeation. [ABSTRACT FROM AUTHOR]