Rational Design and Synthesis of Right-Handed <scp>d</scp>-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein–Protein Interactions

Sang, Peng; Shi, Yan; Higbee, Pirada; Wang, Minghui; Abdulkadir, Sami; Lu, Ji; Daughdrill, Gary W.; Chen, Jiandong; Cai, Jianfeng

doi:10.1021/acs.joc.0c00996

Cited by 19 publications

(28 citation statements)

References 31 publications

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“…Besides inhibiting the p53–hDM2 interactions, β 3 -peptide has also been developed to serve as HIV fusion inhibitors. They further developed a β 3 -decapeptide with a non-natural trifluoromethylbenzene side chain that inhibited the HIV gp41-mediated fusion with a CC 50 /EC 50 ratio of 8, a major improvement compared to previous works. , Cai et al developed an impressive class of sulfono-γ-AApeptides that can reproducibly fold into well-defined helical structures. − They demonstrated that these sulfono-γ-AApeptide helices were excellent mimicries of α-helices in several therapeutically relevant protein–protein interactions and could serve as inhibitors or agonists to these interactions, such as BCL9-β-catenin, p53-MDM2/MDMX, and glucagon peptide-GLP-1R. − …”

Section: Functional Applications Of Sequence-controlled Polymersmentioning

confidence: 99%

Geared Toward Applications: A Perspective on Functional Sequence-Controlled Polymers

Yang

et al. 2021

ACS Macro Lett.

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Sequence-controlled polymers are an emerging class of synthetic polymers with a regulated sequence of monomers. In the past decade, tremendous progress has been made in the synthesis of polymers, with the sophisticated sequence control approaching the level manifested in biopolymers. In contrast, the exploration of novel functions that can be achieved by controlling synthetic polymer sequences represents an emerging focus in polymer science. This Viewpoint will survey recent advances in the functional applications of sequence-controlled polymers and provide a perspective on the challenges and outlook for pursuing future applications of this fascinating class of macromolecules.

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Section: Functional Applications Of Sequence-controlled Polymersmentioning

confidence: 99%

Geared Toward Applications: A Perspective on Functional Sequence-Controlled Polymers

Yang

et al. 2021

ACS Macro Lett.

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“…The above sulfono-γ-AApeptides are left-handed sequences, which attracts the curiosity of researchers to develop the D-sulfono-γ-AApeptide right-handed helical foldamers (Sang et al, 2020a ). As the enantiomers of known left-handed L-sulfono-γ-AApeptides, they could be accomplished by the similar strategy for synthesis.…”

Section: Examples Of Peptide-based Ppi Inhibitorsmentioning

confidence: 99%

Rational Design of Peptide-Based Inhibitors Disrupting Protein-Protein Interactions

Wang

Liu

et al. 2021

Front. Chem.

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Protein-protein interactions (PPIs) are well-established as a class of promising drug targets for their implications in a wide range of biological processes. However, drug development toward PPIs is inevitably hampered by their flat and wide interfaces, which generally lack suitable pockets for ligand binding, rendering most PPI systems “undruggable.” Here, we summarized drug design strategies for developing peptide-based PPI inhibitors. Importantly, several quintessential examples toward well-established PPI targets such as Bcl-2 family members, p53-MDM2, as well as APC-Asef are presented to illustrate the detailed schemes for peptide-based PPI inhibitor development and optimizations. This review supplies a comprehensive overview of recent progresses in drug discovery targeting PPIs through peptides or peptidomimetics, and will shed light on future therapeutic agent development toward the historically “intractable” PPI systems.

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“…Based on the well-documented crystal structure of supramolecular complexes between known ligands and interested proteins, a series of β-peptide-based protein inhibitors were rationally designed and validated. − By displaying functional epitopes of interested proteins on the helical surface of the β-peptide scaffold, diverse ligands with nanomolar affinities were obtained. , Analogously, α-helix-mimicking sulfono-γ-AApeptides (oligomers of γ-substituted- N -acylated- N -aminoethyl amino acid) were designed as potent inhibitors of protein–protein interactions. − The study at a cellular level indicated that such sulfono-γ-AApeptide inhibitors were cell-permeable and could effectively inhibit the proliferation of cancer cells …”

Section: Sdp-based Functional Biomaterialsmentioning

confidence: 99%

Sequence-Defined Synthetic Polymers for New-Generation Functional Biomaterials

Deng

Shi

Tan

et al. 2021

ACS Materials Lett.

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Synthetic polymers have been extensively exploited for biomedical and pharmacological applications, spanning from surgical devices, diagnostics, tissue engineering, regenerative medicine, to drug delivery systems. However, a fundamental and quantitative correlation between the primary chemical structures of polymeric biomaterials and the resulting biological responses remains elusive. Encouragingly, the advent and development of sequence-defined polymers (SDPs) provide an unprecedented opportunity to precisely tune their sequence information, intrachain folding, interchain self-assembly, and macroscopic properties, enabling the elucidation of the structure–property relationship of biomaterials. In this Perspective, we highlight recent advances of SDPs as next-generation functional biomaterials, and their potential applications in antimicrobial agents, bioactive ligands, precision drug delivery systems, bioimaging agents, and barcoded biomaterials, from sequence-defined synthetic oligomers and polymers. Finally, we present a critical outlook on the challenges in the design and development of SDP-based emergent biomaterials.

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Rational Design and Synthesis of Right-Handed d-Sulfono-γ-AApeptide Helical Foldamers as Potent Inhibitors of Protein–Protein Interactions

Cited by 19 publications

References 31 publications

Geared Toward Applications: A Perspective on Functional Sequence-Controlled Polymers

Geared Toward Applications: A Perspective on Functional Sequence-Controlled Polymers

Rational Design of Peptide-Based Inhibitors Disrupting Protein-Protein Interactions

Sequence-Defined Synthetic Polymers for New-Generation Functional Biomaterials

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