Purine nucleotides are vital for RNA and DNA synthesis, signaling, metabolism, and energy homeostasis. To synthesize purines, cells use two principal routes: the de novo and salvage pathways. Traditionally, it is believed that proliferating cells predominantly rely on de novo synthesis, whereas differentiated tissues favor the salvage pathway. Unexpectedly, we find that adenine and inosine are the most effective circulating precursors for supplying purine nucleotides to tissues and tumors, while hypoxanthine is rapidly catabolized and poorly salvaged in vivo. Quantitative metabolic analysis demonstrates comparative contribution from de novo synthesis and salvage pathways in maintaining purine nucleotide pools in tumors. Notably, feeding mice nucleotides accelerates tumor growth, while inhibiting purine salvage slows down tumor progression, revealing a crucial role of the salvage pathway in tumor metabolism. These findings provide fundamental insights into how normal tissues and tumors maintain purine nucleotides and highlight the significance of purine salvage in cancer.

In this work, a covalent organic framework (TADM-COF) with high crystallinity and large specific surface area (2597 m2 g-1) has been successfully synthesized using 1,3,5-(4-aminophenyl) benzene (TAPB) and 2,5-dimethoxy-p-phenyldiformaldehyde (DMTP). The COF was grown in situ on oxide particles to form core-shell nanocomposites (SiO2@TADM COF, Fe3O4@TADM COF and Co3O4@TADM COF) to realize its function as a shell material. Among them, the Co3O4@TADM COF with the highest electrochemical response to purine bases was further cross-linked with multi-walled carbon nanotubes (MWCNT) to construct a novel electrochemical sensor (Co3O4@TADM COF/MWCNT/GCE) for detection of purine bases. In this nanocomposite, Co3O4 possesses rich catalytic active sites, MWCNT ensures superior electrical conductivity and COF provides a stable environment for electrocatalytic reactions as the shell. At the same time, regular pore structure of the COFs also offers smooth channels for the transfer of analytes to the catalytic site. The synergistic effect among the three components showed remarkable sensing performance for the simultaneous detection of guanine (G) and adenine (A) with a wide linear range of 0.6-180 μM and low limits of detection (LODs) of 0.020 μM for G and 0.024 μM for A (S/N = 3), respectively. The developed sensor platform was also successfully applied in the detection of purine bases in thermally denatured herring DNA extract. The work provided a general strategy for amplifying signal of COF and its composite in the electrochemical sensing.

It is of great significance to propose simple methods to detect DNA bases sensitively for biological analysis and medical diagnosis. Herein, a highly crystalline polyimide covalent organic framework (TAPM-COF) has been successfully synthesized via a solvothermal route using pyromellitic dianhydride (PMDA) and tris(4-aminophenyl) amine (TAPA), which possessed large specific surface area (2286 m2 g-1) and excellent thermal stability. Intriguingly, the crystallinity of the TAPM-COF improved significantly with the increase of water content in the reaction medium. To verify this phenomenon, we synthesized TPPM-COF with two pores by pyromellitic dianhydride (PMDA) and N,N,N\',N\'-tetrakis(4-aminophenyl)-1,4-benzenediamine (TPDA), which bonding was similar to TAPM-COF. Furthermore, the prepared TAPM-COF-0.3 was used to construct a novel and independent electrochemical biosensor on glassy carbon electrode for simultaneously determination of adenine (A) and guanine (G) without other additives. However, to further improve signal of TAPM-COF in electrochemical sensing, the crystalline TAPM-COF-0.3 can be readily integrated with amino-functionalized multiwalled carbon nanotubes (NH2-MWCNT) to form core-shell TAPM-COF-0.3@NH2-MWCNT driven by a π-π stacking interaction for more sensitive electrochemical sensing toward purine bases. In comparison to TAPM-COF/GCE, the TAPM-COF@NH2-MWCNT/GCE exhibited more favorable linear range and lower limit of detection. The work provided a new strategy for amplifying signal of COF in the field of electrochemical sensors.

Oligonucleotides containing modified nucleobases have applications in various technologies. In general, to synthesize oligonucleotides with different nucleobase structures, each modified phosphoramidite monomer needs to be prepared over multiple steps and then introduced onto the oligonucleotides, which is time-consuming and inefficient. Post-synthetic modification is a powerful strategy for preparing many types of modified oligonucleotides, especially nucleobase-modified ones. Depending on the stage of modification, post-synthetic modification can be divided into two stages: \"solid-phase modification,\" wherein an oligonucleotide attaches to the resin, and \"solution-phase modification,\" wherein an oligonucleotide detaches itself from the resin. In this review, we focus on post-synthetic modification in solution for the synthesis of nucleobase-modified oligonucleotides, except the modifications to linkers for conjugation. Moreover, the reactions are summarized for each modified position of the nucleobases.

Abiotic synthesis of nucleobases and amino acids is of critical importance as it sheds light on potential prebiotic chemical reactions. During thermal decomposition of formamide in vacuum conditions, purine, cytosine, adenine, hypoxanthine, uracil, pterin, urea, urocanic acid, glycine, alanine and norvaline were detected. The compounds were obtained without catalyst by heating at 100-180 °C or microwave heating of formamide. Reaction network of self-catalyzed chemical reactions is suggested, showing how from only one parent molecule, nucleobases, urea and the amino acid glycine can be produced. The reaction pathways are theoretically determined using SCS-MP2 calculations.Communicated by Ramaswamy H. Sarma.

Introducing purine bases to P2-ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitory because of the carbonyl and NH groups promoting the formation of extensive H-bonding interactions. In this work, thirty-three compounds are synthesized and evaluated, among which inhibitors 16a, 16f and 16j containing N-2-(6-substituted-9H-purin-9-yl)acetamide as the P2-ligands along with 4-methoxylphenylsulfonamide as the P2\'-ligand, display potent inhibitory effect on the activity of HIV-1 protease with IC50 43 nM, 42 nM and 68 nM in vitro, respectively.