Synthetic and natural cyclic peptides provide a testing ground for studying membrane permeability in non-traditional drug scaffolds. Cyclic peptomers, which incorporate peptide and N-alkylglycine (peptoid) residues, combine the stereochemical and geometric complexity of peptides with the functional group diversity accessible to peptoids. I will present structure-property relationships in cyclic peptomer libraries synthesized by split-pool techniques permuting side chain functionality and backbone geometry, and will report on trends that relate lipophilicity (both calculated and measured) to membrane permeability as well as metabolic clearance. I will also present the synthesis of a &gt;250,000-member cyclic peptide library using one-bead-one-compound techniques, and our experimental and computational methods for decoding individual beads selected for target binding.

Simple ADME rules for complex molecules and life beyond the rule of 5

253rd National Meeting (2017)

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