Cyclic Penta- and Hexaleucine Peptides without N-Methylation Are Orally Absorbed.
ACS Med Chem Lett
; 5(10): 1148-51, 2014 Oct 09.
Article
em En
| MEDLINE
| ID: mdl-25313329
ABSTRACT
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 N-methyl amino acids and few hydrogen bond donors. Here we report that cyclic penta- and hexa-leucine peptides, with no N-methylation and five or six amide NH protons, exhibit some degree of oral bioavailability (4-17%) approaching that of the heavily N-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 N-methylation or modified amino acids.
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01-internacional
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MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2014
Tipo de documento:
Article