The novel positively charged pro-drugs of peptides and related compounds in the general formula (1) 'Structure 1' were designed and synthesized. The compounds of the general formula (1) 'Structure 1' indicated above can be prepared by standard peptide synthesis protocols. The positively charged amino group of the pro-drug of peptides not only makes the drugs soluble in water, but also bonds to the negative charge on the phosphate head group of membranes and pushes the pro-drug into the cytosol. The lipophilic portion (by modification of the polar groups with lipophilic alkyl groups) of the prodrugs will facilitate the entering of the drugs into the skin membrane. The results suggest that the pro-drugs diffuses through human skin ~100-1000 times faster than do peptides and related compounds. In plasma, more than 40% of these pro-drugs can change back to the parent drugs in a few minutes. The prodrugs can be used medicinally in treating any peptides and related compounds-treatable conditions in humans or animals. The prodrugs can be administered transdermally for any kind of medical treatments and avoid proteolysis by proteolytic enzymes in the GI tract. Controlled transdermal administration systems of the prodrug enables peptides and related compounds to reach constantly optimal therapeutic blood levels to increase effectiveness and reduce the side effects of peptides and related compounds. Another great benefit of transdermal administration of these pro-drugs is that administering medication, especially to children, will be much easier.
