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Cyclic Peptides

Synthetic methods


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

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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. 

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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

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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.

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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.

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Synthetic Receptors


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

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Cucurbit[7]uril-Tetramethylrhodamine Conjugate for Direct Sensing and Cellular Imaging

A single-component sub-nanomolar optical sensor

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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

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