Understanding the Effects of Ligand Configuration on Protoporphyrinogen IX Oxidase with Rationally Designed 3-(N-Phenyluracil)but-2-enoates.

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is a promising target for green herbicide discovery. However, the ligand configuration effects on PPO activity were still poorly understood. Herein, we designed 3-(N-phenyluracil)but-2-enoates using our previously developed active fragments exchange and link (AFEL) approach and synthesized a series of novel compounds with nanomolar ranges of Nicotiana tabacum PPO (NtPPO) inhibitory potency and promising herbicidal potency. Our systematic structure-activity relationship investigations showed that the E isomers of 3-(N-phenyluracil)but-2-enoates displayed improved bioactivity than their corresponding Z isomers. Using molecular simulation studies, we found that the E isomers showed a relatively lower entropy change and could sample more stable binding conformation to the receptor than the Z isomers. Our density functional theory (DFT) calculations showed that the E isomers showed higher chemical reactivity and lower electronic chemical potential than their corresponding Z isomers. Compound E-Ic emerged as the optimal compound with a Ki value of 3.0 nM against NtPPO, exhibiting a broader spectrum of weed control than saflufenacil at 37.5-75 g ai/ha and also safe to maize at 75 g ai/ha, which could be considered as a promising lead herbicide for further development.

A case report on rapid development of simultaneous liver and musculature calcifications in severe sepsis.

A 76-year-old Malay female presented with 2 days history of fever and vomiting. She was found to have Escherichia coli and Klebsiella pneumoniae bacteraemia with no clear intra-abdominal cause on the initial computed tomography of the abdomen and pelvis (CTAP). She clinically improved with 2 weeks duration of intravenous meropenem. She subsequently developed septic shock and a repeated CTAP demonstrated increased hepatic parenchymal density with extensive parenchymal calcifications. Curvilinear calcifications were seen in the paraspinal and pelvic musculature.

A Rare Case of Small Bowel Obstruction in a 15-Year-Old Girl: Internal Hernia Associated with Meckel's Diverticulum.

BACKGROUND Meckel's diverticulum is a congenital remnant of the omphalomesenteric duct and is the most common congenital gastrointestinal malformation. Most patients are asymptomatic, but a rare presentation is with subacute small bowel obstruction (SBO) due to herniation of bowel loops through an internal hernia formed by the Meckel's diverticulum and adjacent mesentery that forms an internal hernia. This report is of a 15-year-old girl presenting as an emergency with vomiting and small bowel obstruction due to an internal hernia associated with Meckel's diverticulum. CASE REPORT We present a case of a 15-year-old girl who presented to the Children's Emergency (CE) department with persistent vomiting and abdominal distension and tenderness. X-rays demonstrated dilated small bowel loops, prompting admission under Pediatric Surgery (PAS). A subsequent computed tomography (CT) scan was performed, which demonstrated multiple dilated small bowel loops, confirming SBO, and a blind-ending "C-shaped" bowel loop at the region of the terminal ileum. A diagnostic laparotomy was performed, which confirmed the presence of a Meckel's diverticulum. The tip of the Meckel's diverticulum was adherent to part of the small bowel mesentery, forming an internal hernia defect through which a loop of proximal ileum had herniated, resulting in SBO. She then underwent a laparoscopy-assisted transumbilical Meckel's diverticulectomy (LATUM). The patient recovered uneventfully and was discharged on the 4th postoperative day. CONCLUSIONS In children presenting with SBO, the possibility of Meckel's diverticulum as an etiology should be considered as a differential diagnosis. Early diagnosis and prompt intervention will improve clinical outcomes and avoid complications.

Study on the Anti-Mycobacterium marinum Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactone Derivatives.

With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. Mycobacterium marinum, as a model organism of Mycobacterium tuberculosis, can be used for the rapid and efficient screening of bioactive compounds. The 14-membered resorcylic acid lactones (RALs) have a wide range of bioactivities such as antibacterial, antifouling and antimalarial activity. In order to further study their bioactivities, we initially constructed a 14-membered RALs library, which contains 16 new derivatives. The anti-M. marinum activity was evaluated in vitro. Derivatives 12, 19, 20 and 22 exhibited promising activity with MIC90 values of 80, 90, 80 and 80 µM, respectively. The preliminary structure-activity relationships showed that the presence of a chlorine atom at C-5 was a key factor to improve activity. Further studies showed that 12 markedly inhibited the survival of M. marinum and significantly reduced the dosage of positive drugs isoniazid and rifampicin when combined with them. These results suggest that 12 is a bioactive compound capable of enhancing the potency of existing positive drugs, and its effective properties make it a very useful leads for future drug development in combating TB resistance.

Neonatal Nucleus Accumbens Microstructure Modulates Individual Susceptibility to Preconception Maternal Stress in Relation to Externalizing Behaviors.

OBJECTIVE: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems. METHOD: K-means longitudinal cluster analysis was performed to determine trajectories of maternal stress measures (Perceived Stress Scale [PSS], hair cortisol) from preconception to the third trimester. Neonatal NAcc microstructural measures (orientation density index [ODI] and intracellular volume fraction [ICVF]) were compared across trajectories. We then examined the interaction between maternal stress and neonatal NAcc microstructure on child internalizing and externalizing behaviors, assessed between ages 3 and 4 years. RESULTS: Two trajectories of maternal stress magnitude ("low"/"high") were identified for both PSS (n = 287) and hair cortisol (n = 336). Right neonatal NAcc ODI (rNAcc-ODI) was significantly lower in "low" relative to "high" PSS trajectories (n = 77, p = .04). PSS at preconception had the strongest association with rNAcc-ODI (r = 0.293, p = .029). No differences in NAcc microstructure were found between hair cortisol trajectories. A significant interaction between preconception PSS and rNAcc-ODI on externalizing behavior was observed (n = 47, p = .047). CONCLUSION: Our study showed that the preconception period contributes to in utero NAcc development, and that NAcc microstructure modulates individual susceptibility to preconception maternal stress in relation to externalizing problems.

Screen time, brain network development and socio-emotional competence in childhood: moderation of associations by parent-child reading.

BACKGROUND: Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent-child reading in mitigating the effects of screen time. METHODS: We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent-child reading time was a moderator of the link between screen time and brain network topology. RESULTS: Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent-child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (ß = -0.640, p = 0.005). CONCLUSION: Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent-child reading in moderating the association between screen time and topological brain restructuring in early childhood.

Coexpression of TP53, BIM, and PTEN Enhances the Therapeutic Efficacy of Non-Small-Cell Lung Cancer.

For non-small-cell lung cancer (NSCLC), the ubiquitous occurrence of concurrent multiple genomic alterations poses challenges to single-gene therapy. To increase therapeutic efficacy, we used the branch-PCR method to develop a multigene nanovector, NP-TP53-BIM-PTEN, that carried three therapeutic gene expression cassettes for coexpression. NP-TP53-BIM-PTEN exhibited a uniform size of 104.8 ± 24.2 nm and high serum stability. In cell transfection tests, NP-TP53-BIM-PTEN could coexpress TP53, BIM, and PTEN in NCI-H1299 cells and induce cell apoptosis with a ratio of up to 94.9%. Furthermore, NP-TP53-BIM-PTEN also inhibited cell proliferation with a ratio of up to 42%. In a mouse model bearing an NCI-H1299 xenograft tumor, NP-TP53-BIM-PTEN exhibited a stronger inhibitory effect on the NCI-H1299 xenograft tumor than the other test vectors without any detectable side effects. These results exhibited the potential of NP-TP53-BIM-PTEN as an effective and safe multigene nanovector to enhance NSCLC therapy efficacy, which will provide a framework for genome therapy with multigene combinations.

In situ high-valued transformation of nonmetals in waste printed circuit boards into supercapacitor electrodes with excellent performance.

Nonmetals in waste printed circuit boards after metal separation containing brominated resin and fiberglass are considered hazardous and low-recoveryvalue e-waste. However, if these nonmetals are not treated or are improperly treated, they can cause serious environmental pollution. Therefore, there is an urgent and significant need to develop an efficient recycling process for these nonmetals. Based on the concept of high-valued recycling of waste, this study in situ utilized such nonmetals to prepare a porous supercapacitor electrode through a facile carbonization, activation, and carbon thermal reduction process. The results indicated that the activation was a key role in constructing a porous structure. The optimal parameters for activation were a temperature of 800 °C, mass ratio of KOH to pyrolytic residues of 2, and an activation time of 1 h. The electrode materials exhibited a surface area of 589 m2 g-1 and hierarchical porous structures. In addition, the supercapacitors exhibited a capacitance of 77.14 mF cm-2 (62.5 mF cm-2) at 0.5 mA cm-2 (100 mV s-1). Moreover, the supercapacitors had excellent temperature resistance and adaptability. The capacitance retention was 89.36% and 90% at -50 °C and 100 °C after 10 000 cycles, respectively. This study provides a high-valued recycling strategy to utilize the nonmetals in e-waste as energy materials.

Insight into the Role of an α-Helix Cluster in Protoporphyrinogen IX Oxidase.

Protoporphyrinogen IX oxidase (PPO) is the last common enzyme in chlorophyll and heme biosynthesis pathways. In humans, point mutations on PPO are responsible for the dominantly inherited disorder disease variegate porphyria (VP). It is found that several VP-causing mutation sites are located on an α-helix cluster (consisting of α-5, α-6, and α-7 helix, named the G169 helix cluster) of human PPO, although these mutation sites are outside the active site of the human PPO. In this work, we investigated the role of the G169 helix cluster via site-directed mutagenesis, enzymatic kinetics, and computational studies. Kinetic studies showed that mutations on the G169 helix cluster affect the activity of PPO. The MD simulation showed that mutations on the G169 helix cluster reduced the activity of PPO by affecting the proper orientation of substrate protoporphyrinogen within the active site of PPO and possibly the dipole moment of the G169 helix cluster. Moreover, the mutation abolished the interaction between the mutated site and other residues, thus affecting the secondary structure and hydrogen bond interactions within the G169 helix cluster. These results indicated that the integrity of the G169 helix cluster is important for the stabilization of protoporphyrinogen within the active site of PPO to facilitate the interaction between protoporphyrinogen and cofactor FAD and provide a proper electrostatic environment for the activity of PPO. Our result provides new insight into understanding the relationship between the structure and function of PPO.

Cell senescence induced by toxic interaction between α-synuclein and iron precedes nigral dopaminergic neuron loss in a mouse model of Parkinson's disease.

Cell senescence has been implicated in the pathology of Parkinson's disease (PD). Both abnormal α-synuclein aggregation and iron deposition are suggested to be the triggers, facilitators, and aggravators during the development of PD. In this study, we investigated the involvement of α-synuclein and iron in the process of cell senescence in a mouse model of PD. In order to overexpress α-syn-A53T in the substantia nigra pars compacta (SNpc), human α-syn-A53T was microinjected into both sides of the SNpc in mice. We found that overexpression of α-syn-A53T for one week induced significant pro-inflammatory senescence-associated secretory phenotype (SASP), increased cell senescence-related proteins (ß-gal, p16, p21, H2A.X and γ-H2A.X), mitochondrial dysfunction accompanied by dysregulation of iron-related proteins (L-ferritin, H-ferritin, DMT1, IRP1 and IRP2) in the SNpc. In contrast, significant loss of nigral dopaminergic neurons and motor dysfunction were only observed after overexpression of α-syn-A53T for 4 weeks. In PC12 cells stably overexpressing α-syn-A53T, iron overload (ferric ammonium citrate, FAC, 100 µM) not only increased the level of reactive oxygen species (ROS), p16 and p21, but also exacerbated the processes of oxidative stress and cell senescence signalling induced by α-syn-A53T overexpression. Interestingly, reducing the iron level with deferoxamine (DFO) or knockdown of transferrin receptor 1 (TfR1) significantly improved both the phenotypes and dysregulated proteins of cell senescence induced by α-syn-A53T overexpression. All these evidence highlights the toxic interaction between iron and α-synuclein inducing cell senescence, which precedes nigral dopaminergic neuronal loss in PD. Further investigation on cell senescence may yield new therapeutic agents for the prevention or treatment of PD.

Gut microbiota-induced CXCL1 elevation triggers early neuroinflammation in the substantia nigra of Parkinsonian mice.

Gut microbiota disturbance and systemic inflammation have been implicated in the degeneration of dopaminergic neurons in Parkinson's disease (PD). How the alteration of gut microbiota results in neuropathological events in PD remains elusive. In this study, we explored whether and how environmental insults caused early neuropathological events in the substantia nigra (SN) of a PD mouse model. Aged (12-month-old) mice were orally administered rotenone (6.25 mg·kg-1·d-1) 5 days per week for 2 months. We demonstrated that oral administration of rotenone to ageing mice was sufficient to establish a PD mouse model and that microglial activation and iron deposition selectively appeared in the SN of the mice prior to loss of motor coordination and dopaminergic neurons, and these events could be fully blocked by microglial elimination with a PLX5622-formulated diet. 16 S rDNA sequencing analysis showed that the gut microbiota in rotenone-treated mice was altered, and mice receiving faecal microbial transplantation (FMT) from ageing mice treated with rotenone for 2 months exhibited the same pathology in the SN. We demonstrated that C-X-C motif chemokine ligand-1 (CXCL1) was an essential molecule, as intravenous injection of CXCL1 mimicked almost all the pathology in serum and SN induced by oral rotenone and FMT. Using metabolomics and transcriptomics analyses, we identified the PPAR pathway as a key pathway involved in rotenone-induced neuronal damage. Inhibition of the PPARγ pathway was consistent in the above models, whereas its activation by linoleic acid (60 mg·kg-1·d-1, i.g. for 1 week) could block these pathological events in mice intravenously injected with CXCL1. Altogether, these results reveal that the altered gut microbiota resulted in neuroinflammation and iron deposition occurring early in the SN of ageing mice with oral administration of rotenone, much earlier than motor symptoms and dopaminergic neuron loss. We found that CXCL1 plays a crucial role in this process, possibly via PPARγ signalling inhibition. This study may pave the way for understanding the "brain-gut-microbiota" molecular regulatory networks in PD pathogenesis. The aged C57BL/6 male mice with rotenone intragastric administration showed altered gut microbiota, which caused systemic inflammation, PPARγ signalling inhibition and neuroinflammation, brain iron deposition and ferroptosis, and eventually dopaminergic neurodegeneration in PD.

Co-application of Brassinolide and Pyraclostrobin Improved Disease Control Efficacy by Eliciting Plant Innate Defense Responses in Arabidopsis thaliana.

Applying brassinolide (BL, a phytohormone) in combination with pyraclostrobin (Pyr, a fungicide) has shown effective disease control in field trials. However, the mechanism by which BL + Pyr control disease remains uncertain. This work compared the disease control and defense responses of three pretreatments (BL, Pyr, and BL + Pyr) in Arabidopsis thaliana. We found that BL + Pyr improved control against Pyr-sensitive Hyaloperonospora arabidopsidis and Botrytis cinerea by 19 and 17% over Pyr, respectively, and achieved 29% control against Pyr-resistant B. cinerea. Furthermore, BL + Pyr outperformed BL or Pyr in boosting transient H2O2 accumulation, and the activities of POD, APX, GST, and GPX. RNA-seq analysis revealed a more potent activation of defense genes elicited by BL + Pyr than by BL or Pyr. Overall, BL + Pyr controlled disease by integrating the elicitation of plant innate disease resistance with the fungicidal activity of Pyr.

Design, synthesis, and cell-based in vitro assay of deoxyinosine-mixed SATE-dCDN prodrugs that activate all common STING variants.

Developing therapeutic strategies to modulate the activity of all prevalent variants (wild-type, HAQ, R232H, AQ, and R293Q) of the stimulator of interferon genes (STING) is still of great interest to treating immune-related diseases. Herein, we synthesized six novel deoxyinosine-mixed deoxyribose cyclic dinucleotide prodrugs (SATE-dCDN) including a combination of hypoxanthine and other bases (A, U, C, T, and G) for a cell-based in vitro assay. The HPLC assay indicated that deoxyinosine-mixed SATE (S-acylthioalkyl ester)-dCDN prodrugs retained high serum stability. The IRF3-responsive luciferase assay in THP1-Lucia cells showed that the activity of the prodrugs with purine bases (SATE-3',3'-c-di-dIMP, SATE-3',3'-c-di-dIdAMP, and SATE-3',3'-c-di-dIdGMP) was higher than that of the prodrugs with pyrimidine bases (SATE-3',3'-c-di-dIdUMP, SATE-3',3'-c-di-dIdTMP, and SATE-3',3'-c-di-dIdCMP), among which prodrug 14a (SATE-3',3'-c-di-dIdAMP) with hypoxanthine and adenine bases exhibited the highest activity with an EC50 value of 0.046 µM. The IRF3 responsive dual-luciferase reporter assay in HEK293T cells transfected with plasmids expressing different STING variants further showed that prodrug 14a could activate all five most common hSTING variants, including the refractory hSTINGR232H and hSTINGQ variants. Furthermore, prodrug 14a also induced the production of the highest levels of mRNA of IFN-ß, CXCL10, IL-6 and TNF-α through STING-dependent IRF and NF-κB signaling pathways in THP-1 cells. These results suggested that the combination of deoxyinosine with a SATE-dCDN prodrug could modulate the broad-spectrum activity of all common STING variants.

Artificial Intelligence Applications for Osteoporosis Classification Using Computed Tomography.

Osteoporosis, marked by low bone mineral density (BMD) and a high fracture risk, is a major health issue. Recent progress in medical imaging, especially CT scans, offers new ways of diagnosing and assessing osteoporosis. This review examines the use of AI analysis of CT scans to stratify BMD and diagnose osteoporosis. By summarizing the relevant studies, we aimed to assess the effectiveness, constraints, and potential impact of AI-based osteoporosis classification (severity) via CT. A systematic search of electronic databases (PubMed, MEDLINE, Web of Science, ClinicalTrials.gov) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 39 articles were retrieved from the databases, and the key findings were compiled and summarized, including the regions analyzed, the type of CT imaging, and their efficacy in predicting BMD compared with conventional DXA studies. Important considerations and limitations are also discussed. The overall reported accuracy, sensitivity, and specificity of AI in classifying osteoporosis using CT images ranged from 61.8% to 99.4%, 41.0% to 100.0%, and 31.0% to 100.0% respectively, with areas under the curve (AUCs) ranging from 0.582 to 0.994. While additional research is necessary to validate the clinical efficacy and reproducibility of these AI tools before incorporating them into routine clinical practice, these studies demonstrate the promising potential of using CT to opportunistically predict and classify osteoporosis without the need for DEXA.

Multi-Omics Analysis Reveals Synergistic Enhancement of Nitrogen Assimilation Efficiency via Coordinated Regulation of Nitrogen and Carbon Metabolism by Co-Application of Brassinolide and Pyraclostrobin in Arabidopsis thaliana.

Improving nitrogen (N) assimilation efficiency without yield penalties is important to sustainable food security. The chemical regulation approach of N assimilation efficiency is still less explored. We previously found that the co-application of brassinolide (BL) and pyraclostrobin (Pyr) synergistically boosted biomass and yield via regulating photosynthesis in Arabidopsis thaliana. However, the synergistic effect of BL and Pyr on N metabolism remains unclear. In this work, we examined the N and protein contents, key N assimilatory enzyme activities, and transcriptomic and metabolomic changes in the four treatments (untreated, BL, Pyr, and BL + Pyr). Our results showed that BL + Pyr treatment synergistically improved N and protein contents by 56.2% and 58.0%, exceeding the effects of individual BL (no increase) or Pyr treatment (36.4% and 36.1%). Besides synergistically increasing the activity of NR (354%), NiR (42%), GS (62%), and GOGAT (62%), the BL + Pyr treatment uniquely coordinated N metabolism, carbon utilization, and photosynthesis at the transcriptional and metabolic levels, outperforming the effects of individual BL or Pyr treatments. These results revealed that BL + Pyr treatments could synergistically improve N assimilation efficiency through improving N assimilatory enzyme activities and coordinated regulation of N and carbon metabolism. The identified genes and metabolites also informed potential targets and agrochemical combinations to enhance N assimilation efficiency.

A Terphenyllin Derivative CHNQD-00824 from the Marine Compound Library Induced DNA Damage as a Potential Anticancer Agent.

With the emergence of drug resistance and the consequential high morbidity and mortality rates, there is an urgent need to screen and identify new agents for the effective treatment of cancer. Terphenyls-a group of aromatic hydrocarbons consisting of a linear 1,4-diaryl-substituted benzene core-has exhibited a wide range of biological activities. In this study, we discovered a terphenyllin derivative-CHNQD-00824-derived from the marine compound library as a potential anticancer agent. The cytotoxic activities of the CHNQD-00824 compound were evaluated against 13 different cell lines with IC50 values from 0.16 to 7.64 µM. Further study showed that CHNQD-00824 inhibited the proliferation and migration of cancer cells, possibly by inducing DNA damage. Acridine orange staining demonstrated that CHNQD-00824 promoted apoptosis in zebrafish embryos. Notably, the anti-cancer effectiveness was verified in a doxycin hydrochloride (DOX)-induced liver-specific enlargement model in zebrafish. With Solafinib as a positive control, CHNQD-00824 markedly suppressed tumor growth at concentrations of 2.5 and 5 µM, further highlighting its potential as an effective anticancer agent.

Phosphorescence enhancement of pyridinium macrocycles by poly(vinylalcohol).

A phosphorescence enhancement of pyridinium macrocycle/monomer phosphors is realized with up to 14.7-fold prolonging of the phosphorescence lifetimes and visible afterglow by doping into a poly(vinylalcohol) (PVA) matrix. The abundant hydrogen-bonding interactions and electrostatic interactions between the phosphors and the PVA suppressed the nonradiative decay processes, slowed down the radiative decay and nonradiative decay of triplet states, and therefore promoted the long-lived RTP.

Discovery of Benzothiazolylpyrazole-4-Carboxamides as Potent Succinate Dehydrogenase Inhibitors through Active Fragment Exchange and Link Approach.

Succinate dehydrogenase (SDH) is an attractive target for developing green fungicides to manage agricultural pathogens in modern agriculture research. Herein, in this work, we report the discovery of benzothiazolylpyrazole-4-carboxamides I-III as potent SDH inhibitors using active fragment exchange and link approach. The results of the fungicidal activity assays showed that some of the synthesized compounds exhibited excellent inhibition against the tested fungi. Systematic structure-activity relationship studies led to the discovery of compound Ip, N-(1-((4,6-difluorobenzo[d]thiazol-2-yl)thio)propan-2-yl)-3-(difluoromethyl)-N-methoxy-1-methyl-1H-pyrazole-4-carboxamide, which showed higher fungicidal activity against Fusarium graminearum Schw (EC50 = 0.93 µg/mL) than the commercial fungicides thifluzamide (EC50 > 50 µg/mL) and boscalid (EC50 > 50 µg/mL). The molecular simulation studies suggested that hydrophobic interactions were the primary driving forces between ligands and SDH. Promisingly, we found that Ip could stimulate the growth of wheat seedlings and Arabidopsis thaliana and increase the biomass of the treated plants. Preliminary studies on the plant growth promoter mechanism of Ip indicated that it could increase nitrate reductase activity in planta, that, in turn, stimulates the growth of plants.

Suppression of alpha-carbon racemization in peptide synthesis based on a thiol-labile amino protecting group.

In conventional solid-phase peptide synthesis (SPPS), α-amino groups are protected with alkoxycarbonyl groups (e.g., 9-fluorenylmethoxycarbonyl [Fmoc]). However, during SPPS, inherent side reactions of the protected amino acids (e.g., α-C racemization and aspartimide formation) generate by-products that are hard to remove. Herein, we report a thiol-labile amino protecting group for SPPS, the 2,4-dinitro-6-phenyl-benzene sulfenyl (DNPBS) group, which is attached to the α-amino group via a S-N bond and can be quantitatively removed in minutes under nearly neutral conditions (1 M p-toluenethiol/pyridine). The use of DNPBS greatly suppresses the main side reactions observed during conventional SPPS. Although DNPBS SPPS is not as efficient as Fmoc SPPS, especially for synthesis of long peptides, DNPBS and Fmoc are orthogonal protecting groups; and thus DNPBS SPPS and Fmoc SPPS can be combined to synthesize peptides that are otherwise difficult to obtain.