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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Anti-Cancer Peptides: Status and Future Prospects

Molecules, Journal Year: 2023, Volume and Issue: 28(3), P. 1148 - 1148

Published: Jan. 23, 2023

The dramatic rise in cancer incidence, alongside treatment deficiencies, has elevated to the second-leading cause of death globally. increasing morbidity and mortality this disease can be traced back a number causes, including treatment-related side effects, drug resistance, inadequate curative tumor relapse. Recently, anti-cancer bioactive peptides (ACPs) have emerged as potential therapeutic choice within pharmaceutical arsenal due their high penetration, specificity fewer effects. In contribution, we present general overview literature concerning conformational structures, modes action membrane interaction mechanisms ACPs, well provide recent examples successful employment targeting ligands treatment. use ACPs diagnostic tool is summarized, advantages these applications are highlighted. This review expounds on main approaches for peptide synthesis along with reconstruction modification needed enhance effect. Computational that could predict efficacy suggest ACP candidates experimental studies discussed. Future research prospects rapidly expanding area also offered.

Language: Английский

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Peptide-based drug discovery through artificial intelligence: towards an autonomous design of therapeutic peptides

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(4)

Published: May 23, 2024

Abstract With their diverse biological activities, peptides are promising candidates for therapeutic applications, showing antimicrobial, antitumour and hormonal signalling capabilities. Despite advantages, face challenges such as short half-life, limited oral bioavailability susceptibility to plasma degradation. The rise of computational tools artificial intelligence (AI) in peptide research has spurred the development advanced methodologies databases that pivotal exploration these complex macromolecules. This perspective delves into integrating AI development, encompassing classifier methods, predictive systems avant-garde design facilitated by deep-generative models like generative adversarial networks variational autoencoders. There still challenges, need processing optimization careful validation models. work outlines traditional strategies machine learning model construction training techniques proposes a comprehensive AI-assisted pipeline. evolving landscape using is emphasized, showcasing practicality methods expediting discovery novel within context peptide-based drug discovery.

Language: Английский

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Process Mass Intensity (PMI): A Holistic Analysis of Current Peptide Manufacturing Processes Informs Sustainability in Peptide Synthesis

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(7), P. 4261 - 4282

Published: March 20, 2024

Small molecule therapeutics represent the majority of FDA-approved drugs. Yet, many attractive targets are poorly tractable by small molecules, generating a need for new therapeutic modalities. Due to their biocompatibility profile and structural versatility, peptide-based possible solution. Additionally, in past two decades, advances peptide design, delivery, formulation, devices have occurred, making peptides an modality. However, manufacturing is often limited solid-phase synthesis (SPPS), liquid phase (LPPS), lesser extent hybrid SPPS/LPPS, with SPPS emerging as predominant platform technology synthesis. involves use excess solvents reagents which negatively impact environment, thus highlighting newer technologies reduce environmental footprint. Herein, fourteen American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR) member companies portfolio compiled Process Mass Intensity (PMI) metrics help inform sustainability efforts This includes PMI assessment on 40 synthetic processes at various development stages pharma, classified according phase. most comprehensive date. The process was divided into (synthesis, purification, isolation) determine respective PMI. On average, (SPPS) (PMI ≈ 13,000) does not compare favorably other modalities such molecules median 168–308) biopharmaceuticals 8300). Thus, high warrants more environmentally friendly manufacturing.

Language: Английский

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N,N‐Dimethyl Formamide European Restriction Demands Solvent Substitution in Research and Development

ChemSusChem, Journal Year: 2024, Volume and Issue: 17(8)

Published: Jan. 10, 2024

Abstract As of December 2023, the use common solvent N , ‐dimethyl formamide (DMF) will be restricted in European Union because its reproductive health hazard. Industrial facilities must comply with stricter exposure limits, and researchers are recommended to find alternative solvents. Here we explain restrictions on DMF, which disciplines affected, how substitute DMF keep research development commercially relevant.

Language: Английский

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Inverse Peptide Synthesis Using Transient Protected Amino Acids

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(6), P. 4270 - 4280

Published: Feb. 5, 2024

Peptide therapeutics have experienced a rapid resurgence over the past three decades. While few peptide drugs are biologically produced, most manufactured via chemical synthesis. The cycle of prior protection amino group an α-amino acid, activation its carboxyl group, aminolysis with free growing chain, and deprotection N-terminus constitutes principle conventional C → N mandatory use Nα-protecting invokes two additional operations for incorporating each resulting in poor step- atom-economy. burgeoning demand therapeutic market necessitates cost-effective environmentally friendly manufacturing strategies. Inverse synthesis using unprotected acids has been proposed as ideal appealing strategy. However, it remained unsuccessful 60 years due to severe racemization/epimerization during chain elongation. Herein, this challenge successfully addressed by ynamide coupling reagent employing transient activation, protection, aminolysis, situ were performed one pot, thus offering practical strategy formally starting material. Its robustness was exemplified syntheses active pharmaceutical ingredients. It is also amenable fragment condensation inverse solid-phase compatibility green solvents further enhances application potential large-scale production. This study offered cost-effective, operational convenient, benign approach peptides.

Language: Английский

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Ynamide Coupling Reagents: Origin and Advances

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(6), P. 855 - 869

Published: March 7, 2024

ConspectusSince the pioneering work of Curtius and Fischer, chemical peptide synthesis has witnessed a century's development evolved into routine technology. However, it is far from perfect. In particular, challenged by sustainable because state-of-the-art heavily relies on legacy reagents technologies developed before establishment green chemistry. Over past three decades, broad range efforts have been made for greening synthesis, among which using unprotected amino acid represents an ideal promising strategy does not require protection deprotection steps. Unfortunately, C → N employing acids plagued undesired polymerization, while inverse with retarded severe racemization/epimerization owing to iterative activation aminolysis high susceptible peptidyl acids. Consequently, there urgent need develop innovative coupling strategies novel mechanisms that can address long-standing notorious issue synthesis.This Account will describe our in discovery ynamide their application synthesis. eight-year journey, class general both amide ester bond formation. superiority suppressing enabled them be effective fragment condensation, head-to-tail cyclization, as well precise incorporation thioamide substitutions backbones. The first practical was successfully accomplished harnessing such features taking advantage transient strategy. Ynamide reagent-mediated formation efficient intermolecular esterification macrolactonization preservation α-chirality configuration conjugated α,β-C–C double bond. To make readily available reasonable cost convenience, we scalable one-step synthetic method cheap starting materials. Furthermore, water-removable reagent developed, offering column-free purification target product. addition, recycle accomplished, thereby paving way industrial application.As such, this presents whole story origin, mechanistic insights, preparation, applications, perspective highlights future impact

Language: Английский

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Exploring FDA-Approved Frontiers: Insights into Natural and Engineered Peptide Analogues in the GLP-1, GIP, GHRH, CCK, ACTH, and α-MSH Realms

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 264 - 264

Published: Feb. 22, 2024

Peptides continue to gain significance in the pharmaceutical arena. Since unveiling of insulin 1921, Food and Drug Administration (FDA) has authorised around 100 peptides for various applications. Peptides, although initially derived from endogenous sources, have evolved beyond their natural origins, exhibiting favourable therapeutic effectiveness. Medicinal chemistry played a pivotal role synthesising valuable peptide analogues, providing synthetic alternatives with potential. Furthermore, key chemical modifications enhanced stability strengthened interactions targets. For instance, selective extended half-life lessened frequency administration while maintaining desired action. In this review, I analyse FDA approval peptides, as well engineered diabetes treatment, growth-hormone-releasing hormone (GHRH), cholecystokinin (CCK), adrenocorticotropic (ACTH), α-melanocyte stimulating (α-MSH) analogues. Attention will be paid structure, mode action, developmental journey, authorisation, adverse effects these peptides.

Language: Английский

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Recent advances, strategies, and future perspectives of peptide-based drugs in clinical applications

Chinese Journal of Natural Medicines, Journal Year: 2025, Volume and Issue: 23(1), P. 31 - 42

Published: Jan. 1, 2025

Language: Английский

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Active ester-based peptide bond formation and its application in peptide synthesis

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(7), P. 1817 - 1846

Published: Jan. 1, 2023

Active ester method is an efficient strategy to address the notorious racemization/epimerization issue of peptide bond formation. Herein, pros and cons using active esters for synthesis were systematically summarized analyzed.

Language: Английский

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