Photo-induced radical thiol–ene chemistry: a versatile toolbox for peptide-based drug design

Ahangarpour, Marzieh; Kavianinia, Iman; Harris, Paul W. R.; Brimble, Margaret A.

doi:10.1039/d0cs00354a

Cited by 49 publications

(36 citation statements)

References 392 publications

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“…It is superior to semaglutide [33,42] and insulin degludec [33,43]. The main critical improvements are modification of residues in the peptide backbone to obtain GIP receptor-activating activity, prolongation of the C-terminus with a sequence of C-terminal of exenatide, and conjugation of the fatty acid side chain to prolong half-life (116.7 h) [30,44]. In addition, hepatoprotection cannot be overlooked [45].…”

Section: Structure and Activitymentioning

confidence: 99%

Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review

Chavda¹,

Ajabiya

Teli

et al. 2022

Molecules

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The prevalence of obesity and diabetes is an increasing global problem, especially in developed countries, and is referred to as the twin epidemics. As such, advanced treatment approaches are needed. Tirzepatide, known as a ‘twincretin’, is a ‘first-in-class’ and the only dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) receptor agonist, that can significantly reduce glycemic levels and improve insulin sensitivity, as well as reducing body weight by more than 20% and improving lipid metabolism. This novel anti-diabetic drug is a synthetic peptide analog of the human GIP hormone with a C20 fatty-diacid portion attached which, via acylation technology, can bind to albumin in order to provide a dose of the drug, by means of subcutaneous injection, once a week, which is appropriate to its a half-life of about five days. Tirzepatide, developed by Eli Lilly, was approved, under the brand name Mounjaro, by the United States Food and Drug Administration in May 2022. This started the ‘twincretin’ era of enormously important and appealing dual therapeutic options for diabetes and obesity, as well as advanced management of closely related cardiometabolic settings, which constitute the leading cause of morbidity, disability, and mortality worldwide. Herein, we present the key characteristics of tirzepatide in terms of synthesis, structure, and activity, bearing in mind its advantages and shortcomings. Furthermore, we briefly trace the evolution of this kind of medical agent and discuss the development of clinical studies.

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Section: Structure and Activitymentioning

confidence: 99%

Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review

Chavda¹,

Ajabiya

Teli

et al. 2022

Molecules

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“…The reversibility and using amine or phosphine catalysts in Thia‐Michael additions caused some difficulties in industrialization, whereas the thiol–ene reaction is more general in industrial processes. The molecular weight of acceptable polythioether ranges in 500–2000 g/mol, preferably between 1000–10,000 g/mol, and desirably in 2000–5000 g/mol 1,6 …”

Section: Introductionmentioning

confidence: 99%

“…The molecular weight of acceptable polythioether ranges in 500-2000 g/mol, preferably between 1000-10,000 g/mol, and desirably in 2000-5000 g/mol. 1,6 There are few investigations around the elasticity and mechanical properties of polythioethers. Ruiyi et al 7 synthesized some different polythioether from cyclic and acyclic dienes and investigated their thermal resistance.…”

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confidence: 99%

Designing a novel polythioether/multiwall carbon nanotube nanocomposites: A complete overview of mechanical, thermal, and morphological properties

Haramshahi

Jazani

Sohrabian

2022

Polymers for Advanced Techs

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Polythioether is an elastomer with proper thermal resistance and elongation at break, which can be used in various high-temperature and high-pressure sealing applications. This research is aimed to determine the suitable thiol/vinyl ratio and the branching agent content to synthesize a novel polythioether and the polythioether/ multiwall carbon nanotube (MWCNT) composite using two monomers, including dimercapto dioxaoctane (DMDO) and triethylene glycol divinylether. For each synthesis process, the gel permeation chromatography (GPC) was used to measure the molecular weight and the polydispersity index of the polymer chains. Fourier transforms infrared spectroscopy and Nuclear Magnetic Resonance were used to study the bond formation, while the glass transition of the polymer was evaluated by differential scanning calorimetry. Tensile and lap adhesion tests were also used to assess the mechanical properties of the samples. Field emission scanning electron microscopy was utilized to observe the dispersion of nanoparticles in polythioether/ MWCNT nanocomposite. GPC results showed that the thiol/vinyl ratio of 0.5 and branching agent molar ratio of 0.2 (relative to vinyl monomer) led to the most suitable average molecular weight (2022 g/mol) which had the highest mechanical properties.The nanocomposite containing 1 wt% MWCNT, showed the highest tensile strength and elongation at break up to 2.12 MPa and 303%, respectively. A considerable increase of 30 C is obtained in maximum degradation temperature of the produced nanocomposite compared to neat polythioether.

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“…Hydrothiolation has been known in literature since the early 1900s, when it was mentioned in the studies concentrated on photo-curable resins as well as protective coatings. [9] Thiol-ene reaction is the addition of thiol groups to unsaturated C=C bonds in alkenes, leading to the formation of a thioether bond. [10] This reaction belongs to the "click chemistry" due to the high yields, a relatively short reaction time and the absence or minimal content of by-products as well as the use of mild, commercially available reagents.…”

Section: Introductionmentioning

confidence: 99%

Sulfur‐Containing Silsesquioxane Derivatives Obtained by the Thiol‐ene Reaction: Synthesis and Thermal Degradation

et al. 2022

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This article presents the synthesis of new derivatives of octa(3thiopropyl)silsesquioxane (SSQ-8SH) via thiol-ene reaction with simple olefins bearing alkyl groups as well as methoxysilyl, substituted aryl or fluoroalkyl groups. All products were characterized by 1 H NMR, 13 C NMR, 29 Si NMR, FTIR, GPC, MALDI-TOF-MS, as well as thermal analysis (TGA) to confirm their structures, purity and thermal stability, and finally give some insight into their thermal degradation pathway. In some of the structures obtained, the T 5% values take place at high temperatures and are close to 230 °C. The thiol-ene reaction allowed to obtain 7 new compounds with high yield (> 92 %), no byproducts and in a relatively short time (24 h). All products are characterized by high conversion > 99 %. New derivatives can find potential use as modifiers of plastics to improve their certain properties for example hydrophobicity or thermooxidative stability.

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Photo-induced radical thiol–ene chemistry: a versatile toolbox for peptide-based drug design

Abstract: Thiol–ene chemistry, a tailored approach to access novel peptide-based drugs.

Cited by 49 publications

References 392 publications

Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review

Tirzepatide, a New Era of Dual-Targeted Treatment for Diabetes and Obesity: A Mini-Review

Designing a novel polythioether/multiwall carbon nanotube nanocomposites: A complete overview of mechanical, thermal, and morphological properties

Sulfur‐Containing Silsesquioxane Derivatives Obtained by the Thiol‐ene Reaction: Synthesis and Thermal Degradation

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