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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FDA's stamp of approval: Unveiling peptide breakthroughs in cardiovascular diseases, ACE, HIV, CNS, and beyond

Journal of Peptide Science, Journal Year: 2024, Volume and Issue: unknown

Published: June 17, 2024

Peptides exhibit significant specificity and effective interaction with therapeutic targets, positioning themselves as key players in the global pharmaceutical market. They offer potential treatments for a wide range of diseases, including those that pose challenges. Notably, peptide trofinetide (Daybue) marked groundbreaking achievement by providing first-ever cure Rett syndrome, several peptides have secured FDA approval first-in-class medications. Furthermore, are expanding their presence areas traditionally dominated either small or large molecules. A noteworthy example is motixafortide (Aphexda) first peptide-based chemokine antagonist. Here, focus will be on analysis FDA-approved peptides, particularly targeting cardiovascular human immunodeficiency, central nervous system various other intriguing classes addressing conditions such osteoporosis, thrombocytopenia, Cushing's disease, hypoglycemia, among others. The review explore chemical structures indications modes action, developmental trajectory, adverse effects.

Language: Английский

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Peptides, solid-phase synthesis and characterization: Tailor-made methodologies

Electronic Journal of Biotechnology, Journal Year: 2023, Volume and Issue: 64, P. 27 - 33

Published: May 4, 2023

Solid-Phase Peptide Synthesis (SPPS) is a mature technique widely used in research and production. There are different approaches that fulfill the diverse requirements, regarding number, quantity quality of peptides. We have implemented three laboratory protocols synthesis cover these needs. These been tested, results analyzed with two sequences previous works. The peptide such as tea bag, microwave manual allowed obtaining specific yields 8, 43 64% for NBC112 36, 46 78% NBC759 protocols, respectively. Each protocol has application contexts advantages disadvantages each case. allow obtention peptides good purity can be according to needs requirements. This article includes an interactive 360-degree video. To view it correctly, necessary scroll through screen navigate across where you will find 10 points. For immersive experience, head-mounted display used. Please, visit this URL: http://ejbiotechnology.info/public/360view/2023/VTPCARDENAS1v1/index.html. How cite: Guzmán F, Aróstica M, Román T, et al. Peptides, solid-phase characterization: Tailor-made methodologies. Electron J Biotechnol 2023;64. https://doi.org/10.1016/j.ejbt.2023.01.005.

Language: Английский

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A Novel Method for Liraglutide Synthesis and Purification

Peptide Science, Journal Year: 2024, Volume and Issue: 116(5)

Published: May 3, 2024

ABSTRACT Liraglutide, developed by Novo Nordisk, is applied in Type 2 diabetes and obesity treatment. Several solid‐phase peptide synthesis protocols were designed for its production. However, current are expensive many of them difficult to scale‐up. In this study, a novel alternative liraglutide production was developed. The elongated Fmoc/tBu on 4‐hydroxymethylbenzoyl–ChemMatrix (HMBA‐CM) resin using the chaotropic agent LiCl as an additive prevent aggregation. After elongation, removal side‐chain protecting groups cleavage from performed two‐stage procedure. Side‐chain removed with 92.5% TFA, leaving unprotected attached solid support. thoroughly washed eliminate contaminants. Next, release achieved treating peptidyl NaOH 0.1 N. This procedure assures high‐purity product without need large amount ether previous protocols. Finally, purified hydrophobic interaction low‐pressure liquid chromatography (HI‐LPLC) instead RP‐HPLC reported methods. simple economic method resulted high yield purity while overcoming cost difficulties processes.

Language: Английский

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Peptides and metal ions: A successful marriage for developing artificial metalloproteins

Journal of Peptide Science, Journal Year: 2024, Volume and Issue: unknown

Published: May 8, 2024

The mutual relationship between peptides and metal ions enables metalloproteins to have crucial roles in biological systems, including structural, sensing, electron transport, catalytic functions. effort reproduce or/and enhance these roles, or even create unprecedented functions, is the focus of protein design, first step toward comprehension complex machinery nature. Nowadays, design allows building sophisticated scaffolds, with novel functions exceptional stability. Recent progress metalloprotein has led peptides/proteins capable orchestrating desired different cofactors. structural diversity proper selection first- second-shell ligands, as well long-range electrostatic hydrophobic interactions, which represent precious tools for tuning properties. scope this review discuss construction sites de novo designed miniaturized scaffolds. Selected examples mono-, di-, multi-nuclear binding sites, from last 20 years will be described an highlight key artificial models electron-transfer metalloproteins. authors' goal make readers feel like guests at marriage while offering sources inspiration future architects innovative,

Language: Английский

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Unnatural Amino Acids: Strategies, Designs, and Applications in Medicinal Chemistry and Drug Discovery

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(22), P. 19932 - 19965

Published: Nov. 11, 2024

Peptides can operate as therapeutic agents that sit within a privileged space between small molecules and larger biologics. Despite examples of their potential to regulate receptors modulate disease pathways, the development peptides with drug-like properties remains challenge. In quest optimize physicochemical parameters improve target selectivity, unnatural amino acids (UAAs) have emerged critical tools in peptide- peptidomimetic-based drugs. The utility UAAs is illustrated by clinically approved drugs such methyldopa, baclofen, gabapentin addition drug molecules, for example, bortezomib sitagliptin. this Perspective, we outline strategy deployment FDA-approved targets. We further describe modulation using UAAs. Finally, elucidate how these improved pharmacological role played impact progress analogs preclinical stages an emphasis on

Language: Английский

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Fmoc Solid-Phase Peptide Synthesis

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown, P. 33 - 55

Published: Jan. 1, 2024

Language: Английский

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Advances in Therapeutic Peptides Separation and Purification

Separations, Journal Year: 2024, Volume and Issue: 11(8), P. 233 - 233

Published: July 29, 2024

Peptides are gaining prominence in various fields, including the pharmaceutical industry. To meet regulatory requirements, they must achieve a certain purity threshold to ensure safe administration. Numerous purification technologies have been employed purify peptides, aiming reduce cost and time while being sustainable efficient. These include chromatography, magnetic nanoparticles, isoelectric focusing, membrane filtration. The physicochemical properties of peptides main driving element behind these technologies. While chromatographic separation remains gold standard for peptide purification, with models predict elution behaviors other demonstrated their capability performance established methodologies, better productivity reduced cost. This opens door further investigational studies assess outcomes potentially introduce new techniques purification. In this review, we examine terms efficiency ability sustainability concluding remarks an outlook on future advancements.

Language: Английский

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N‐ to C‐Peptide Synthesis, Arguably the Future for Sustainable Production

Journal of Peptide Science, Journal Year: 2025, Volume and Issue: 31(6)

Published: May 1, 2025

A revolution in peptide production arrived from the innovation of carboxylate to amine C- N-direction solid-phase synthesis. This cornerstone modern science has enabled multiple academic and industrial applications; however, process N-solid phase synthesis (C-N-SPPS) extreme mass intensity poor atom economy. Notably, C-N-SPPS relies upon use atom-intensive protecting groups, such as fluorenylmethyloxycarbonyl (Fmoc) protection wasteful excess protected amino acids coupling agents. On other hand, N- C-direction offers potential minimize may arguably enable more efficient means for manufacturing peptides. For example, amide bond formation been accomplished using methods employing thioesters, vinyl esters, transamidation achieve with minimal epimerization. review aims provide an overview C-peptide indicating advantages taking this avenue sustainable production.

Language: Английский

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