Marekebisho ya usahihi ya peptidi zilizo na cysteine ​​au protini kwa kutumia chumvi za alkylthiophenium

Kemia ya bioorthogonal, kama njia inayotumika kwa urekebishaji wa kuchagua wa molekuli za kibayolojia chini ya hali ndogo ya kisaikolojia, has attracted the attention of the scientific community in recent years due to its wide range of applications and far-reaching impact. Hata hivyo, reactive groups (k.m., alkynyl, azide, tetrazine, nk.) in conventional click chemistry are extremely rare in natural biomolecules, making the introduction of these groups a challenging task. Cysteine (Cys) is widely present in peptides and proteins, and it is estimated that about 2% of cysteine (Cys) is present in natural products.This amino acid, which is relatively abundant in proteins and is rich in thiol groups, provides an SH site for the modification of peptides and proteins, based on which an orthogonal chemical modification strategy based on alkyl thiophenium salts has been developed by the research organization.

Technical Highlights

• Highly selective: Alkyl thiophenium salts are able to directly and selectively orthogonally modify cysteine residues via S_N2 reaction, a process that takes place under mild conditions with high chemoselectivity and compatibility.
• Multifunctional modification: The technology is capable of introducing a wide range of functional structures, including PEG chains, fluorescent molecules, drugs, carboboranes, carbohydrates, and peptides, greatly enriching the functionality of biomolecules.
• Multifunctional biocoupling: The study further reveals that the technology enables multifunctional biocoupling by introducing clickable “handles” such as alkynes and azides. This means that a variety of complex biocouplings can be flexibly assembled in a “two-step, one-pot” reaction, further broadening the scope of biomodification applications.
• Successful application to proteins: The application of this technology to complex proteins has also been validated. Scientists successfully labeled bovine serum albumin (BSA) using alkylthioindigo salts, demonstrating the universality and effectiveness of the method in complex biomolecules.

The orthogonal biocoupling technique based on alkylthiophenium salts is an efficient and precise modification method, which provides a powerful tool for efficient and specific modification of peptides and proteins, and has a broad application prospect.

Xiaoxia Chen

Dawa Mpya R&D Fundi Utaalamu wa Msingi: Ugunduzi unaolengwa, uhusiano wa shughuli za muundo (SAR) uchambuzi, viunganishi vya peptide-dawa (PDCs), na maendeleo ya peptidi za kupambana na kuzeeka na kimetaboliki.

Kuhusu Mwandishi Machapisho ya Hivi Punde

Wasifu: Xiaoxia Chen ameongoza ugunduzi wa mapema na utafiti wa mapema wa dawa kadhaa za kimetaboliki na peptidi zinazolengwa na tumor.. Yeye sio tu mahiri katika uchunguzi wa hali ya juu wa maktaba za peptidi lakini pia ana ustadi wa kutumia baiolojia ya hesabu inayosaidiwa na AI kwa muundo wa mfuatano wa peptidi ya de novo.. Kwa sasa, anaongoza timu inayojitolea kwa utafiti wa kina na ukuzaji wa wahusika wengi wa kizazi kijacho. (kama vile mbili- au peptidi za kupunguza mafuta zinazolengwa mara tatu) na peptidi za kutengeneza tishu zenye kazi sana.

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