Peptides as Therapeutic Agents: Challenges and Opportunities in the Green Transition Era

Molecules, Journal Year: 2023, Volume and Issue: 28(20), P. 7165 - 7165

Published: Oct. 19, 2023

Peptides are at the cutting edge of contemporary research for new potent, selective, and safe therapeutical agents. Their rise has reshaped pharmaceutical landscape, providing solutions to challenges that traditional small molecules often cannot address. A wide variety natural modified peptides have been obtained studied, many others advancing in clinical trials, covering multiple therapeutic areas. As demand peptide-based therapies grows, so does need sustainable environmentally friendly synthesis methods. Traditional peptide synthesis, while effective, involves draining processes, generating significant waste consuming vast resources. The integration green chemistry offers alternatives, prioritizing eco-friendly reduction, energy conservation. This review delves into transformative potential applying principles by discussing relevant examples application such approaches production active ingredients (APIs) with a structure how these efforts critical an effective transition era field.

Language: Английский

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Evolutionary origins and interactomes of human, young microproteins and small peptides translated from short open reading frames

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(6), P. 994 - 1011.e18

Published: Feb. 17, 2023

All species continuously evolve short open reading frames (sORFs) that can be templated for protein synthesis and may provide raw materials evolutionary adaptation. We analyzed the origins of 7,264 recently cataloged human sORFs found most were evolutionarily young had emerged de novo. additionally identified 221 previously missed potentially translated into peptides up to 15 amino acids—all which are smaller than smallest microprotein annotated date. To investigate bioactivity sORF-encoded small microproteins, we subjected 266 candidates a mass-spectrometry-based interactome screen with motif resolution. Based on these interactomes additional cellular assays, associate several mRNA splicing, translational regulation, endocytosis. Our work provides insights interaction potential proteins, thereby helping elucidate this underexplored territory proteome.

Language: Английский

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Design of target specific peptide inhibitors using generative deep learning and molecular dynamics simulations

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 21, 2024

We introduce a computational approach for the design of target-specific peptides. Our method integrates Gated Recurrent Unit-based Variational Autoencoder with Rosetta FlexPepDock peptide sequence generation and binding affinity assessment. Subsequently, molecular dynamics simulations are employed to narrow down selection peptides experimental assays. apply this strategy inhibitors that specifically target β-catenin NF-κB essential modulator. Among twelve inhibitors, six exhibit improved compared parent peptide. Notably, best C-terminal binds an IC

Language: Английский

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Liquid-Phase Peptide Synthesis (LPPS): A Third Wave for the Preparation of Peptides

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(16), P. 13516 - 13546

Published: July 11, 2022

Since the last century, peptides have gained wide acceptance as drugs, with almost 100 already in market and a large number pipeline. In this context, peptide synthesis has grown massively stringent field for pharmaceuticals around globe. Three methodologies, namely, classical solution (CSPS), solid-phase (SPPS), liquid-phase (LPPS), made significant contributions to field. This review provides comprehensive integrated vision of LPPS third wave synthesis. combines advantages CSPS SPPS, where elongation is carried out growing chain supported on soluble tag, which confers characteristic properties. protocols allow large-scale production reduce use excess reagents solvents, thus meeting principles green chemistry. review, tags associated are broadly discussed under following headings: polydisperse polyethylene glycol (PEG), membrane-enhanced (MEPS), fluorous technology, ionic liquids (ILs), PolyCarbon, hydrophobic polymers, group-assisted purification (GAP). It also highlights signature accomplishments limitations same.

Language: Английский

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Molecularly Stimuli-Responsive Self-Assembled Peptide Nanoparticles for Targeted Imaging and Therapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(9), P. 8004 - 8025

Published: April 20, 2023

Self-assembly has emerged as an extensively used method for constructing biomaterials with sizes ranging from nanometers to micrometers. Peptides have been investigated self-assembly. They are widely applied owing their desirable biocompatibility, biodegradability, and tunable architecture. The development of peptide-based nanoparticles often requires complex synthetic processes involving chemical modification supramolecular Stimuli-responsive peptide nanoparticles, also termed "smart" capable conformational changes in response stimuli, a class promising materials. These smart find diverse range biomedical applications, including drug delivery, diagnostics, biosensors. systems include external stimuli (such light, temperature, ultrasound, magnetic fields) internal pH, redox environment, salt concentration, biomarkers), facilitating the generation library self-assembled imaging therapy. Thus, this review, we mainly focus on built by self-assembly strategy systematically discuss mechanisms various stimuli. Furthermore, summarize applications nanomaterials, diagnosis therapy, demonstrate potential medical translation.

Language: Английский

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Advancements, challenges and future perspectives on peptide-based drugs: Focus on antimicrobial peptides

European Journal of Pharmaceutical Sciences, Journal Year: 2022, Volume and Issue: 181, P. 106363 - 106363

Published: Dec. 16, 2022

Language: Английский

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Beyond 20 in the 21st Century: Prospects and Challenges of Non-canonical Amino Acids in Peptide Drug Discovery

ACS Medicinal Chemistry Letters, Journal Year: 2023, Volume and Issue: 14(5), P. 557 - 565

Published: April 24, 2023

Life is constructed primarily using a toolbox of 20 canonical amino acids─relying upon these building blocks for the assembly proteins and peptides that regulate nearly every cellular task, including cell structure, function, maintenance. While Nature continues to be source inspiration drug discovery, medicinal chemists are not beholden only acids have begun explore non-canonical (ncAAs) construction designer with improved drug-like properties. However, as our ncAAs expands, hunters encountering new challenges in approaching iterative peptide design–make–test–analyze cycle seemingly boundless set blocks. This Microperspective focuses on technologies accelerating ncAA interrogation discovery (including HELM notation, late-stage functionalization, biocatalysis) while shedding light areas where further investment could accelerate medicines but also improve downstream development.

Language: Английский

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Enantioselective Deaminative Alkylation of Amino Acid Derivatives with Unactivated Olefins

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(3), P. 1130 - 1137

Published: Jan. 14, 2022

Herein, we report the first Ni-catalyzed enantioselective deaminative alkylation of amino acid and peptide derivatives with unactivated olefins. Key for success was discovery a new sterically encumbered bis(oxazoline) ligand backbone, thus offering de novo technology accessing enantioenriched sp3–sp3 linkages via sp3 C–N functionalization. Our protocol is distinguished by its broad scope generality across wide number counterparts, even in context late-stage In addition, an remote hydroalkylation reaction internal olefins within reach, providing useful entry point forging centers at C–H sites.

Language: Английский

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Single-Molecule Junction: A Reliable Platform for Monitoring Molecular Physical and Chemical Processes

ACS Nano, Journal Year: 2022, Volume and Issue: 16(3), P. 3476 - 3505

Published: Feb. 18, 2022

Monitoring and manipulating the physical chemical behavior of single molecules is an important development direction molecular electronics that aids in understanding world at single-molecule level. The electrical detection platform based on junctions can monitor processes level with a high temporal resolution, stability, signal-to-noise ratio. Recently, combination different multimodal control systems has been widely used to explore significant phenomena because its powerful monitoring capabilities. In this review, we focus applications processes. methods developed for characterizing charge transfer spin characteristics as well revealing corresponding intrinsic mechanisms are introduced. Dynamic regulation conformational isomerization, intermolecular interactions, reactions also discussed detail. addition these dynamic investigations, review discusses open challenges fields physics chemistry proposes some potential field.

Language: Английский

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Derivatization with fatty acids in peptide and protein drug discovery

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 22(1), P. 59 - 80

Published: Aug. 24, 2022

Language: Английский

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