Research
Cyclic Peptides
Synthetic methods
Permeability
Therapeutic applications
Abstract 1560: Orally bioavailable macrocycles that target cyclins A and B RxL motifs cause tumor regression in xenograft models and in vitro show activity across multiple cancer types
Using structure-guided design we have developed cell-permeable macrocycle compounds that inhibit the RxL-mediated binding of substrates to both Cyclin A/CDK2 and Cyclin B/CDK1 complexes (Cyclin A/B RxL inhibitors) and have demonstrated that synthetic lethality requires inhibition of both Cyclins A and B
Cyclic Peptide Natural Products Chart the Frontier of Oral Bioavailability in the Pursuit of Undruggable Targets
Cyclic peptides are potentially the future of intracellular protein-protein interaction inhibition. We review intrinsically permeable cyclic peptide therapeutics and model systems.
Beyond Cyclosporine A: Conformation-Dependent Passive Membrane Permeabilities of Cyclic Peptide Natural Products
Natural product permeability is rationalized via computational modeling
Probing the Physicochemical Boundaries of Cell Permeability and Oral Bioavailability in Lipophilic Macrocycles Inspired by Natural Products
Non-proteinogenic backbone elements permit passive permeability and oral bioavailability
Structure-Permeability Relationships in Natural Product-Inspired Cyclic Peptides
PhD dissertation
Cyclative Release of Peptidic Compounds
The present disclosure provides efficient and reliable methods for preparing cyclized peptidic compounds. Advantageously, the currently described methods allow for on-resin cyclization using a limited number of processing steps, while increasing the chemical diversity available for the cyclized peptidic compounds produced.
Chapter 5: Bioactive and Membrane-Permeable Cyclic Peptide Natural Products
A summary of structure-permeability lessons and a survey of the diverse structures observed in bioactive cyclic peptide natural products
Going Out on a Limb: Delineating the Effects of β-branching, N-Methylation, and Side Chain Size on the Permeability, Solubility, and Flexibility of Sanguinamide A Analogs
Lipophilicity and flexibility play important roles in determining the passive permeability of a cyclic peptide natural product
Form and Function of Cyclic Peptide Natural Products: A Pharmacokinetic Perspective
Cyclic peptide natural products adopt solvent-dependent conformations that permit passive permeability.
Synthetic Receptors
Cucurbiturils
Molecular recognition of peptides and proteins
Aromatic interactions
Molecular Recognition of Methionine-Terminated Peptides by Cucurbit[8]uril
Cucurbit[8]uril recognizes methionine-aliphatic side chain pairs with high affinity. No aromatic residue required!
Predictive Recognition of Native Proteins by Cucurbit[7]uril in a Complex Mixture
Selective recognition of proteins with N-terminal Phe residues using a resin-based tool
Cucurbit[7]uril-Tetramethylrhodamine Conjugate for Direct Sensing and Cellular Imaging
A single-component sub-nanomolar optical sensor
Chapter 6: Molecular Recognition of Aromatic Peptides and Proteins in Nature and by Design
The unique properties of aromatic residues afford strong and selective interactions with proteins and synthetic receptors
