Chemical O-ADP-Ribosylations: Synthesis and Bioconjugation of ADPr-Peptides/Proteins from NAD.

ADP-ribosylation is a complex post-translational modification involved in key physiological processes and associated with various health and disease states. The growing interest in ADP-ribosylation necessitates straightforward and efficient synthetic methods for the preparation of ADP-ribosylated peptides/proteins. In this study, we report a facile reaction between nicotinamide adenine dinucleotide (NAD) and alcohols promoted by a combination of ionic liquids, yielding up to 94 % with α : β ratios ranging from 88 : 12 to 99 : 1 and a switchable configuration selectivity.

Recognition and Sequencing of Mutagenic DNA Adduct at Single-Base Resolution Through Unnatural Base Pair.

DNA lesions are linked to cancer, aging, and various diseases. The recognition and sequencing of special DNA lesions are of great interest but highly challenging. In this paper, an unnatural-base-pair-promoting method for sequencing highly mutagenic ethenodeoxycytidine (εC) DNA lesions that occurred frequently is developed.

Solvent-Driven Room-Temperature Curtius Rearrangements to Access Nucleotides Bearing Substituted Fused Pyridones.

The intramolecular Curtius rearrangement suffers from a high reaction temperature, low yields, tedious product isolation, and difficult scale up. This study presents a room-temperature Curtius rearrangement that can be novelly driven by the HFIP solvent, followed by light-illuminated intramolecular cyclization. Such a mild reaction allows for the preparation of various fused pyridone derivatives with diverse substituent groups that have rarely been incorporated by previous methods.

Peripheral substitution effects on unnatural base pairs: A case of brominated TPT3 to enhance replication fidelity.

The high fidelity poses a central role in developing unnatural base pairs (UBPs), which means the high pairing capacity of unnatural bases with their partners, and low mispairing with all the natural bases. Different strategies have been used to develop higher-fidelity UBPs, including optimizing hydrophobic interaction forces between UBPs. Variant substituent groups are allowed to fine tune the hydrophobic forces of different UBPs' candidates.

Designing a Light-Induced Glycosylation Reaction for Poststage Synthesis of ADP-2″-Deoxyribosyl Derivatives.

Modifications on the hydroxyl groups of ADP-ribosyl units can provide valuable tools for investigating ADP-ribosylation-related molecular interactions, but the chemical syntheses of these compounds are usually difficult due to their inherent complex structures. In this study, we report a poststage synthetic protocol for accessing novel ADP-2″-deoxyribosyl derivatives through designing a light-induced biomimetic reaction, and SPR assays revealed effective binding of ADP-2″-deoxyribosyl peptides to MacroH2A1.1 with a high affinity ( = 3.

Locating, tracing and sequencing multiple expanded genetic letters in complex DNA context via a bridge-base approach.

A panel of unnatural base pairs is developed to expand genetic alphabets. One or more unnatural base pairs (UBPs) can be inserted to enlarge the capacity, diversity, and functionality of canonical DNA, so monitoring the multiple-UBPs-containing DNA by simple and convenient approaches is essential. Herein, we report a bridge-base approach to repurpose the capability of determining TPT3-NaM UBPs.

Amplification, Enrichment, and Sequencing of Mutagenic Methylated DNA Adduct through Specifically Pairing with Unnatural Nucleobases.

3-Methylthymine (m3T) is a long-known chemically stable but strongly mutagenic DNA base adduct; however, the sequencing method to determine m3T is lacking so far. Two of the main obstacles include the capacity of m3T to stall DNA elongation and its low abundance. To address the challenges, we report an unnatural base pairing strategy in this paper.

Site-specific unnatural base excision visible light.

Base excision (BE) is an important yet hard-to-control biological event. Unnatural base pairs are powerful tools to revolutionize biological studies in various areas. In this paper, we report a visible-light-induced method to construct site-specific unnatural BE and show the influence of its regulation on transcription and translation levels.

Mechanistic Insight into the Photoinduced Damage of an Unnatural Base Pair.

Chemical- and photostability of unnatural base pairs (UBPs) are important to maintain the genetic code integrity, and critical for developing healthy semisynthetic organisms. As reported, dTPT3 was less stable upon irradiation, and thus might act as a pervasive photosensitizer to induce oxidative damage within DNA, causing harm to living semi-synthetic organisms when exposed to UVA radiation. However, there was no knowledge about molecular-level understanding of this damage process.

Copper-catalyzed oxidative-coupling for one-pot synthesis of 5-aryl-1,4-disubstituted 1,2,3-triazoles under mild conditions.

A new reaction system with CuCl as catalyst, TEA as base and O/chloramine-T as oxidant was developed for one-pot oxidative-coupling to synthesize 5-aryl-1,4-disubstituted 1,2,3-triazoles in this paper. A variety of 5-arylated-1,2,3-triazole compounds could be efficiently prepared directly from the readily accessible organic azides, terminal alkynes and arylboronic acids. Advantages of the method include use of low-cost catalyst, clean oxidant, less-toxic additive, and low reaction temperature.

Access to Photostability-Enhanced Unnatural Base Pairs via Local Structural Modifications.

Completing the storage and retrieval of increased genetic information in vivo and producing therapeutic proteins have been achieved by the unnatural base pair dNaM-dTPT3. Up to now, some biological and chemical approaches are implemented to improve the semi-synthetic organism (SSO). However, the photosensitivity of this pair, suggested as a potential threat to the healthy growth of cells, is still a problem to solve.

Biomimetic α-selective ribosylation enables two-step modular synthesis of biologically important ADP-ribosylated peptides.

The α-type ADP-ribosylated peptides represent a class of important molecular tools in the field of protein ADP-ribosylation, however, they are difficult to access because of their inherent complicated structures and the lack of effective synthetic tools. In this paper, we present a biomimetic α-selective ribosylation reaction to synthesize a key intermediate, α-ADP-ribosyl azide, directly from native β-nicotinamide adenine dinucleotide in a clean ionic liquid system. This reaction in tandem with click chemistry then offers a two-step modular synthesis of α-ADP-ribosylated peptides.

An efficient and easily-accessible ligand for Cu(I)-catalyzed azide-alkyne cycloaddition bioconjugation.

A novel ligand (6) for copper-catalyzed azide-alkyne cycloaddition (CuAAC) in bioconjugation has been developed. Both in vitro and in vivo experiments indicate that 6 is more efficient and less cytotoxic than the canonical CuAAC ligands. Besides, 6 is easily accessible and can be prepared at gram scale.

Light-Responsive, Reversible Emulsification and Demulsification of Oil-in-Water Pickering Emulsions for Catalysis.

Pickering emulsions are an excellent platform for interfacial catalysis. However, developing simple and efficient strategies to achieve product separation and catalyst and emulsifier recovery is still a challenge. Herein, we report the reversible transition between emulsification and demulsification of a light-responsive Pickering emulsion, triggered by alternating between UV and visible light irradiation.

Biocompatible ionic liquid [Betaine][HPO] as a reusable catalyst for the substitution of xanthen-9-ol under solvent-free conditions.

An ionic liquid, namely [Betaine][HPO], was found to be an efficient catalyst for the direct substitution reaction of xanthen-9-ol with different nucleophiles under solvent-free conditions. This catalytic system is easy to be operated and the following work-up procedure is simple, with the ionic liquid catalyst reusable for at least five cycles at a high catalytic activity level. In addition, the ionic liquid is easy to prepare and its raw materials are inexpensive and have good biocompatibility.

Medium Rings Bearing Bitriazolyls: Easily Accessible Structures with Superior Performance as Cu Catalyst Ligands.

Benefiting from their unique properties, the development of structurally novel and easily accessible medium rings is of significant interest in the pharmaceutical industry and academic research. However, synthetic access to medium-ring scaffolds is very difficult due to their rigid skeleton and large-angle strains. In this paper, a new class of medium rings bearing bitriazolyls (MRBTs) was designed, synthesized, identified as a promising new skeleton ligand for the Cu(I)-catalyzed click reaction, and used in site-special modification of protein.

Multicomponent Aqueous Synthesis of Iodo-1,2,3-triazoles: Single-Step Models for Dual Modification of Free Peptide and Radioactive Iodo Labeling.

Iodo-1,2,3-triazoles are of considerable interest for chemical and biomedical applications. However, current synthetic methods for preparing iodo-1,2,3-triazoles cannot easily be applied to the direct modification of bioactive molecules in water. Through the combination of water-compatible oxidative iodination and the copper-catalyzed alkyne-azide cycloaddition reaction, a novel copper-catalyzed aqueous multicomponent synthetic method for the preparation of 5-iodo-1,2,3-triazoles has been developed.

Tuning the Hydrophilicity and Hydrophobicity of the Respective Cation and Anion: Reversible Phase Transfer of Ionic Liquids.

The separation and recycling of catalyst and cocatalyst from the products and solvents are of critical importance. In this work, a class of functionalized ionic liquids (ILs) were designed and synthesized, and by tuning the hydrophilicity and hydrophobicity of cation and anion, respectively, these ILs could reversibly transfer between water and organics triggered upon undergoing a temperature change. From a combination of multiple spectroscopic techniques, it was shown that the driving force behind the transfer was originated from a change in conformation of the PEG chain of the IL upon temperature variation.

A copper(I)-catalyzed three-component domino process: assembly of complex 1,2,3-triazolyl-5-phosphonates from azides, alkynes, and H-phosphates.

Three is better than one! A new copper-catalyzed tricomponent reaction of a terminal alkyne, organic azide, and H-phosphate (CuAA[P]C) leads to a structurally diverse polysubstituted 1,2,3-triazolyl-5-phosphonate, which provides an efficient tool for the direct introduction of phosphonic acid groups by a "click reaction".

A convenient preparation of 5-iodo-1,4-disubstituted-1,2,3-triazole: multicomponent one-pot reaction of azide and alkyne mediated by CuI-NBS.

The system of CuI and NBS was found to provide both I (+) and Cu (+) for the first time. An efficient method for preparation of 5-iodo-1,4-disubstituted-1,2,3-triazole was achieved by multicomponent one-pot reaction of azides with alkynes in the presence of the novel CuI and NBS catalytic system. The high tolerance of various sensitive groups revealed the potential applications of this method in organic synthesis and drug discovery.

Effect of pressure on the selectivity for the esterification of ethylene glycol with propionic acid in supercritical CO2.

The esterification of ethylene glycol with propionic acid was investigated in supercritical CO2 at 50.0 degrees C. The effect of pressure on equilibrium conversion and selectivity of ethylene glycol monopropionate (monoester) and ethylene glycol dipropinonate (diester) was studied systematically.