1 research outputs found
Cyclic Penta- and Hexaleucine Peptides without <i>N</i>‑Methylation Are Orally Absorbed
Development of peptide-based drugs
has been severely limited by
lack of oral bioavailability with less than a handful of peptides
being truly orally bioavailable, mainly cyclic peptides with <i>N</i>-methyl amino acids and few hydrogen bond donors. Here
we report that cyclic penta- and hexa-leucine peptides, with no <i>N</i>-methylation and five or six amide NH protons, exhibit
some degree of oral bioavailability (4–17%) approaching that
of the heavily <i>N</i>-methylated drug cyclosporine (22%)
under the same conditions. These simple cyclic peptides demonstrate
that oral bioavailability is achievable for peptides that fall outside
of rule-of-five guidelines without the need for <i>N</i>-methylation or modified amino acids