Macrocycles: lessons from the distant past, recent developments, and future directions.

ABSTRACT: A noticeable increase in molecular complexity of drug targets has created an unmet need in the therapeutic agents that are larger than traditional small molecules. Macrocycles, which are cyclic compounds comprising 12 atoms or more, are now recognized as molecules that "are up to the task" to interrogate extended protein interfaces. However, because macrocycles (particularly the ones based on peptides) are equipped with large polar surface areas, achieving cellular permeability and bioavailability is anything but straightforward. While one might consider this to be the Achilles' heel of this class of compounds, the synthetic community continues to develop creative approaches toward the synthesis of macrocycles and their site-selective modification. This perspective provides an overview of

SUBMITTER: Yudin AK 

PROVIDER: S-EPMC5424464 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature