Understanding Tetrahydropyranyl as a Protecting Group in Peptide Chemistry

Sharma, Anamika; Ramos-Tomillero, Iván; El‐Faham, Ayman; Nicolás, Ernesto; Rodríguez, Hortensia; Torre, Beatriz G. de la; Alberício, Fernando

doi:10.1002/open.201600156

Cited by 16 publications

(8 citation statements)

References 78 publications

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“…77 More recently, Thp has been explored as a protecting group for additional amino acid residues such as Ser and Thr. 179 5.2.4 tert-Butyl (tBu). The use of the tert-butyl (tBu) group to protect Cys (Fig.…”

Section: Tetrahydropyranyl (Thp)mentioning

confidence: 99%

Cysteine protecting groups: applications in peptide and protein science

2021

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Section: Tetrahydropyranyl (Thp)mentioning

confidence: 99%

Cysteine protecting groups: applications in peptide and protein science

2021

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“…However, even our optimized amidation condition described above was not effective for the coupling of Fmoc-Thr(Trt)-OH with MeVal (37% conversion at 2.5 h and 55% at 6 h) because of the bulkiness of the Trt group and was accompanied by 8% epimerization (entry 2). The choice of THP solved this dilemma, because the coupling of Fmoc-Thr(THP)-OH at 2.5 h achieved over 90% conversion (entry 3, discussion on deprotection by weak acids: vide infra). , The reaction for 6 h achieved 99% conversion with 3% epimerization. We chose the THP group as the protecting group not only for Thr but also for other amino acids with a hydroxy group, such as Ser and MeSer (entry 4 and 5).…”

Section: Resultsmentioning

confidence: 99%

“…The choice of THP solved this dilemma, because the coupling of Fmoc-Thr(THP)-OH at 2.5 h achieved over 90% conversion (entry 3, discussion on deprotection by weak acids: vide infra). 43,44 The reaction for 6 h achieved 99% conversion with 3% epimerization. We chose the THP group as the protecting group not only for Thr but also for other amino acids with a hydroxy group, such as Ser and MeSer (entry 4 and 5).…”

Section: Overcoming the Low Amidation Reactivitymentioning

confidence: 99%

Broadly Applicable and Comprehensive Synthetic Method forN-Alkyl-Rich Drug-like Cyclic Peptides

Nomura¹,

Hashimoto²,

Takeyama³

et al. 2022

J. Med. Chem.

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We report a versatile and durable method for synthesizing highly N-alkylated drug-like cyclic peptides. This is the first reported method for synthesizing such peptides in parallel with a high success rate and acceptable purity that does not require optimizations for a particular sequence. We set up each reaction condition by overcoming the following issues: (1) diketopiperazine (DKP) formation, (2) insufficient peptide bond formation due to the steric hindrance of the N-alkylated amino acid, and (3) instability of highly N-alkylated peptides under acidic conditions. Using this newly established method, we successfully synthesized thousands of cyclic peptides to explore the scope of this modality in drug discovery. We here demonstrate the syntheses of a hundred representative examples, including our first clinical N-alkyl-rich cyclic peptide (LUNA18) that inhibits an intracellular tough target (RAS), in 31% total yield and 97% purity on average after 23 or 24 reaction steps.

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“…Moreover, the THP protecting group can be easily removed under slightly acidic conditions. The advantage of the THP group over the benzyl-based protecting groups is associated with the obtaining of protective compounds with better solubility [ 40 ].…”

Section: Resultsmentioning

confidence: 99%

New Betulin Derivatives with Nitrogen Heterocyclic Moiety—Synthesis and Anticancer Activity In Vitro

et al. 2022

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As part of the search for new medicinal substances with potential application in oncology, the synthesis of new compounds combining the betulin molecule and the indole system was carried out. The structure of the ester derivatives obtained in the Steglich reaction was confirmed by spectroscopic methods (1H and 13C NMR, HR-MS). The obtained new 3-indolyl betulin derivatives were evaluated for anticancer activity against several human cancer cell lines (melanomas, breast cancers, colorectal adenocarcinomas, lung cancer) as well as normal human fibroblasts. The significant reduction in MCF-7 cells viability for 28-hydroxy-(lup-20(29)-ene)-3-yl 2-(1H-indol-3-yl)acetate was observed at a concentration of 10 µg/mL (17 µM). In addition, cytometric analysis showed that this compound strongly reduces the proliferation rate of breast cancer cells. For this, the derivative showing the promising cytotoxic effect on MCF-7 breast cancer cells, the pharmacokinetic profile prediction was performed using in silico methods. Based on the results obtained in the study, it can be concluded that indole-functionalized triterpene EB367 is a promising starting point for further research in the field of breast cancer therapy or the synthesis of new derivatives.

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Understanding Tetrahydropyranyl as a Protecting Group in Peptide Chemistry

Cited by 16 publications

References 78 publications

Cysteine protecting groups: applications in peptide and protein science

Cysteine protecting groups: applications in peptide and protein science

Broadly Applicable and Comprehensive Synthetic Method forN-Alkyl-Rich Drug-like Cyclic Peptides

New Betulin Derivatives with Nitrogen Heterocyclic Moiety—Synthesis and Anticancer Activity In Vitro

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