Widespread use of proteins and peptides in medicine has been limited by their lack of oral bioavailability. This is generally ascribed to poor membrane permeability and metabolic instability. Nevertheless, the use of protein and peptide injectables has developed impressively over the last decade. Traditionally drug companies have relied on simplified models to estimate oral bioavailability for screening of large compound libraries, these include empirical guides like “Rule-Of-Five”, permeability models and models for metabolic stability. These models however have failed to successfully correlate with oral bioavailability of peptides that usually do not fit under the "Rule-Of-Five". Our recent results have shown that compounds considered outliers and oddities in the cyclic peptide chemical space above MW 500 g/mol do not necessarily follow the traditional precept that has dominated past drug discovery. We show that cyclic peptides, even some with poor membrane permeability, can be orally bioavailable even in the absence of N-methylation of amides, which has generally been thought to be necessary for oral absorption.

Orally bioavailable cyclic peptides

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.