Peptide-based drug discovery: Current status and recent advances

Drug Discovery Today, Год журнала: 2022, Номер 28(2), С. 103464 - 103464

Опубликована: Дек. 5, 2022

Язык: Английский

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Contemporary Approaches for Amide Bond Formation

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(24), С. 4359 - 4391

Опубликована: Ноя. 7, 2023

Abstract Amide bond construction has garnered significant interest in recent decades due to amides being one of the most prevalent functional groups among bioactive molecules. Out thirty‐seven new drugs approved by FDA 2022, eleven are small molecules containing at least amide bond. Additionally, there nineteen large as drugs, some which have peptide structures, and therefore, also bear bonds. In years, multiple teams embraced challenge developing more efficient methods for formation. This dedication led numerous publications appearing monthly prestigious journals, showcasing advancements this field. The primary goal review is present viable strategies constructing It crucial differentiate between formation synthesis; hence, focus on describing specific forming C(O)−N particular, concentrates developed within last six years. There a particular emphasis approaches that consider thought process when selecting starting materials groups. approach ensures coverage all common chemical transformations yield

Язык: Английский

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Recent developments in catalytic amide bond formation

Peptide Science, Год журнала: 2020, Номер 112(6)

Опубликована: Ноя. 1, 2020

Abstract Amide bond forming reactions are critical for both polypeptide synthesis and medicinal chemistry. Most current approaches amidation employ stoichiometric activating agents, but such methods neither atom economical nor synthetically elegant. Catalytic potentially green more ideal substitutes standard thus the subject of this review. Such face significant thermodynamic kinetic barriers have, as a result, historically conceded use elevated temperatures dehydrating agents or lacked broad relevant substrate scopes from perspective peptide Recent advancements in direct (the coupling carboxylic acid an amine) indirect other partners resulting amide bond) based on aryl boronic acids, transition metals organocatalysis former ester redox‐coupled later, address these previous shortcomings examined therein.

Язык: Английский

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

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(7), С. 1817 - 1846

Опубликована: Янв. 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.

Язык: Английский

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Direct Catalytic Amidations from Carboxylic Acid and Ester Derivatives: A Review

Catalysts, Год журнала: 2023, Номер 13(2), С. 366 - 366

Опубликована: Фев. 7, 2023

The prevalence of amides in biological systems and chemical fields such as polymers, materials natural products drives continuous research on novel procedures to obtain these ubiquitous functional groups. Currently, efforts this purpose are mainly focused around the discovery direct catalytic methods that more atom economic, safe practical for diversified applications (e.g., organic, medicinal peptide chemistries, material polymer purposes, etc.), accordance with green chemistry principles. field amide synthesis has attained a level significance number reviews articles addressing it grown exponentially last decade. Rather than providing general overview amidation methods, which have been described broadly well recent literature, review is highlight formation bonds from amines carboxylic acids or esters. goal emphasize mechanistic aspects, but also discuss substrate tolerance racemization issues (when applicable).

Язык: Английский

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Heterocyclic Boron Acid Catalyzed Dehydrative Amidation of Aliphatic/Aromatic Carboxylic Acids with Amines

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(5), С. 2832 - 2840

Опубликована: Фев. 15, 2023

A commercially available and versatile dehydrative amidation catalyst, featuring a thianthrene boron acid structure, has been developed. The catalyst shows high catalytic activity to both aliphatic less reactive aromatic carboxylic substrates, including several bioactive or clinical molecules with group.

Язык: Английский

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Direct formation of amide/peptide bonds from carboxylic acids: no traditional coupling reagents, 1-pot, and green

Chemical Science, Год журнала: 2023, Номер 14(13), С. 3462 - 3469

Опубликована: Янв. 1, 2023

Technology for generating especially important amide and peptide bonds from carboxylic acids amines that avoids traditional coupling reagents is described. The 1-pot processes developed rely on thioester formation, neat, using a simple dithiocarbamate, are safe green, Nature-inspired thioesters then converted to the targeted functionality.

Язык: Английский

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Borate-Catalysed Direct Amidation Reactions of Coordinating Substrates

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

A new borate ester amidation catalyst was developed, that shows higher reactivity with challenging carboxylic acids and amines. Reactions could be performed on multigram scale the generated in situ from commercial reagents.

Язык: Английский

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En Route to a Heterogeneous Catalytic Direct Peptide Bond Formation by Zr-Based Metal–Organic Framework Catalysts

ACS Catalysis, Год журнала: 2021, Номер 11(13), С. 7647 - 7658

Опубликована: Июнь 10, 2021

Peptide bond formation is a challenging, environmentally and economically demanding transformation. Catalysis key to circumvent current bottlenecks. To date, many homogeneous catalysts able provide synthetically useful methods have been developed, while heterogeneous remain largely restricted the studies addressing prebiotic of peptides. Here, catalytic activity Zr6-based metal–organic frameworks (Zr-MOFs) toward peptide investigated using dipeptide cyclization as model reaction. Unlike previous catalysts, Zr-MOFs tolerate water, reactions are carried out under ambient conditions. Notably, catalyst recyclable no additives activate COOH group necessary, which common limitations methods. In addition, broad reaction scope tolerates substrates with bulky Lewis basic groups. The mechanism was assessed by detailed mechanistic computational features acid activation carboxylate groups Zr centers amine addition in an alkoxy ligand on adjacent sites assists lowering barrier proton transfers. proposed concepts were also used study intermolecular formation. While intrinsic challenges associated structure water removal limit more general conditions, results suggest that further design Zr-MOF could render these materials broadly for this challenging

Язык: Английский

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Peptide Bond-Forming Reaction via Amino Acid Silyl Esters: New Catalytic Reactivity of an Aminosilane

ACS Catalysis, Год журнала: 2020, Номер 10(16), С. 9594 - 9603

Опубликована: Июль 31, 2020

The epimerization-free formation of peptide bonds is crucial for the development therapeutics and pharmaceuticals. Herein, we report a hydrosilane-mediated approach construction between most amino acids under ambient conditions. This concise protocol with an original silylating reagent HSi(OCH(CF3)2)3 facilitates use bearing broad variety functional groups without any epimerization. Moreover, catalytic system using aminosilane catalyst enables not only acceleration in silylation carboxylic but also amide synthesis minimal substrate (electrophile/nucleophile/silylating = 1:1:1) waste production (hydrogen gas siloxane). These simple powerful approaches are established as potentially general paradigm desired peptides high yields.

Язык: Английский

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