Poly(ethylene glycol) (PEG)-lipids endow lipid nanoparticles (LNPs) with colloidal stability but elicit anti-PEG immunity upon repeat dosing. Here it is replaced PEG-lipids with microbial rhamnolipids (RLs) to create PEG-free, self-adjuvanting LNPs. RL-LNPs show higher than 90% mRNA encapsulation and enhanced dendritic cell uptake via the mannose receptor and DEC205, redirecting expression to lymph nodes after intramuscular injection. Compared with size-matched PEG-LNPs, RL-LNPs enhance transfection and neutralizing capacity against pseudoviruses, while potently amplifying Th1-biased humoral and cytotoxic T-cell responses. Quantitative proteomics and western blotting reveal activation of the C-type lectin receptor (CLR)/NF-kappa B axis, corroborating intrinsic adjuvancy. Notably, RL-LNPs avoid PEG-associated mast-cell infiltration under repeat dosing while maintaining favorable systemic chemistry panels and histology. These data establish glycolipids as dual-function substitutes for PEG-lipids, coupling stabilization with receptor-programmed immunity for next-generation mRNA vaccines.

Prostate cancer ranks among the most prevalent malignancies in males, while current therapies are largely restricted by insufficient targeting, severe systemic toxicity, and acquired drug resistance. The trimethyl lock (TML) platform offers a modular strategy to integrate targeting ligands, therapeutic payloads, and microenvironment‐responsive moieties for precision therapy. Based on this platform, we designed and synthesized a series of reactive oxygen species (ROS)‐responsive small‐molecule drug conjugates (SMDCs) targeting prostate‐specific membrane antigen (PSMA). All six conjugates (SMDC‐1 to SMDC‐6) bound to recombinant PSMA with affinities in nanomolar range and showed antiproliferative activity against PSMA‐positive 22Rv1 cells (IC₅₀: 1.96-65.52 nM) comparable to that of free MMAE in a PSMA‐dependent manner. Based on these results, SMDC‐6 was selected for in vivo evaluation. At a high dose (0.56 mg/kg), SMDC‐6 exhibited antitumor efficacy similar to free MMAE but without inducing body weight loss or significant organ toxicity, demonstrating a markedly improved safety profile. These findings suggest that TML bearing ROS‐responsive SMDCs represent a promising strategy for targeted prostate cancer therapy.

We report a method to selectively etch either component in NaYF4/Fe3O4 binary nanoparticle superlattices using a single etchant. Thermally-induced evolution of oleate ligands on the NaYF4 nanoparticles reverses their relative etching susceptibility in oxalic acid, yielding non-close-packed nanoparticle arrays with tunable architectures.

Lipid nanoparticles (LNPs) are essential for efficient messenger RNA (mRNA) delivery but induce innate inflammation, exhibit limited lymphatic transport, and fail to stimulate adaptive immunity robustly. To address these challenges, we developed quercetin-glucoside derivatives (QG) and introduced them into the LNP system. Among the synthesized derivatives, QG2 (quercetin-di-glucoside) with a 30% molar substitution, maintained optimal nanoparticle stability and enhanced mRNA transfection efficiency in vivo. QG2-LNPs showed increased lymph node transfection, improved dendritic cell activation, and significantly higher SARS-CoV-2 mRNA-driven humoral and cellular immune responses compared to conventional LNPs. Notably, QG2-LNPs substantially reduced local neutrophil infiltration and systemic proinflammatory cytokines while maintaining excellent biocompatibility. These findings highlight quercetin-glucoside as a promising modular design for LNPs that enhances delivery efficiency while reducing inflammatory responses.

Abstract The catalytic performance, depending on the surface nature, is ubiquitous in photocatalysis. However, surface engineering for organic photocatalysts through structural modulation has long been neglected. Here, we propose a zone crystallization strategy for covalent organic frameworks (COFs) that enhances surface ordering through regulator-induced amorphous-to-crystalline transformation. Dynamic simulations show that attaching monofunctional regulators to the surface of spherical amorphous precursor improves surface dynamic reversibility, increasing crystallinity from the inside out. The resulting COF microspheres display surface-enhanced crystallinity and uniform spherical morphology. The visible photocatalytic hydrogen evolution rate reaches 126 mmol g–1 h–1 for the simplest β-ketoenamine-linked COF and 350 mmol gCOF –1 h–1 for SiO2@COF with minimal Pt cocatalysts. Mechanism studies indicate that surface crystalline domains build the surface electrical fields to accumulate photogenerated electrons and diminish electron transfer barriers between the COF and Pt interface. This work bridges the gap between microscopic molecules and macroscopic properties, allowing tailored design of crystalline organic photocatalysts.

We present a general strategy for constructing mechanically robust superlattices using monomicelle-encapsulated nanocrystals (MENCs) as building blocks. MENCs are created by encapsulating individual nanocrystals within micelles of poly(styrene-co-maleic anhydride), driven by hydrophobic interactions between styrene segments and native surface ligands. Concurrent hydrolysis of maleic anhydride moieties generates carboxyl groups that establish intramicelle hydrogen bonds (H-bonds), stabilizing MENCs in aqueous dispersion. Upon solvent evaporation, MENCs self-assemble into long-range-ordered, three-dimensional superlattices. Crucially, postassembly intermicelle H-bonding spontaneously fuses adjacent MENCs into a continuous, cross-linked architecture. This dual-level H-bonding imparts exceptional structural cohesion, yielding superlattices with elastic moduli of up to 18.73 GPa, far exceeding conventional superlattices stabilized by van der Waals or H-bonding interactions.

Although first-line alectinib has prolonged survival in ALK-mutated non-small-cell lung cancers (NSCLCs), the response to treatment varies among patients, and the primary/early development of alectinib resistance mechanisms is still not fully understood. Here, we analyzed molecular profiles of 108 alectinib-treated patients (first-line and second-line after crizotinib) with confirmed relapse by targeted sequencing of cancer-related genes. After first-line treatment, off-target MET and NF2 alterations were more frequent than on-target alterations within the first 6 months, causing primary or early resistance. Conversely, on-target alterations became prevalent after 1 year of first-line alectinib treatment and predominantly after second-line. The incidence of acquired resistance also depended on EML4-ALK variants. In variant 1 (v1), off-target alterations were responsible for 50% of resistance cases after first-line alectinib therapy, whereas on-target mutations had no contribution in this subgroup. In variant 3 (v3), on-target alterations resulted in 46% of resistance cases, whereas only 18% were caused by off-target mutations. After second-line treatment, the most common mutations in v1 were L1196M (42%) and G1269A (25%), while G1202R was detected in 45% of v3 tumors. These findings emphasize the importance of stratifying resistance mechanisms to guide tailored treatment for ALK-positive NSCLCs.

Prostate cancer, a leading malignancy in men globally, faces challenges such as poor targeting, systemic toxicity, and drug resistance. This study developed an innovative multifunctional linker based on the trimethyl lock (TML) system, enabling parallel conjugation of key modules for targeted drug delivery. The linker integrates three functional components: (1) a targeting module (ACUPA), (2) a drug module (docetaxel, DTX), and (3) a trigger module (GSH-responsive disulfide bond). This "three-in-one" design allows flexible adjustment of physicochemical properties. Two conjugates were designed and formulated into nanoparticles. Physicochemical characterization demonstrated their excellent self-assembly and GSH-responsive release properties. Cellular assays showed that the conjugates exhibited comparable inhibitory activity against PSMA-positive 22Rv1 cells to DTX, while their activity against PSMA-negative PC 3 cells was lower. Cellular uptake confirmed higher internalization in 22Rv1 cells than in PC 3 cells. In vivo, low-dose PEG3.4k-TML-DTX nanoparticles (10 mg/kg) achieved tumor inhibition rates similar to free DTX without causing weight loss, demonstrating favorable biosafety. This study provides a novel strategy for targeted chemotherapy with tumor microenvironment responsiveness and low toxicity.

Understanding membrane protein (MP) structure and function is less advanced than that of soluble proteins. Detergents are the primary reagents used in membrane protein studies, yet only a limited selection is employed in both fundamental and applied research. This study presents the design, synthesis, and application of novel triazole-embedded maltose-neopentyl-glycol (TMNG) amphiphiles for membrane protein studies. Utilizing Copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC), the synthesis integrates two maltose hydrophilic subunits with the two-tailed lipid component, overcoming scalability issues encountered in previous methods. Thermal stabilization evaluations show that some TMNGs have equal or improved stabilizing effects compared to the widely used detergent maltose-neopentyl glycol (LMNG).

While there have been advancements in the development of innovative PROTACs with sophisticated linkers designed to meet specific requirements, studies on the structure-activity relationships (SAR) of linker length remain a fundamental priority. Although several reliable chemistries for connecting the two ligands-one targeting the protein and the other for E3 ubiquitin ligase-have been established, the potential for utilizing various other methods still needs exploration. In this work, we introduced a concept that employs the SuFEx reaction, a novel family of click chemistry, to quickly construct a small PROTAC library for protein degradation. This was achieved by amidating a sulfonyl fluoride or fluorosulfate precursor (modified with the p300/CBP ligand CPI644) with CRBN ligands that possess amino-carbon chains of varying lengths. The protein degradation effects of the PROTACs created through this strategy were further validated using the p300/CBP overexpressed MDA-MB-468 cell line.

Covalently linking an adjuvant to an antigenic protein enhances its immunogenicity by ensuring a synergistic delivery to the immune system, fostering a more robust and targeted immune response. Most adjuvant-protein conjugate vaccines incorporate only one adjuvant due to the difficulties in its synthesis. However, there is a growing interest in developing vaccines with multiple adjuvants designed to elicit a more robust and targeted immune response by engaging different aspects of the immune system for complex diseases where traditional vaccines fall short. Here, we pioneer the synthesis of a dual-adjuvants protein conjugate Vaccine 1 by assembling a toll-like receptor 7/8 (TLR7/8) agonist, an invariant natural killer T cell (iNKT) agonist with a clickable bicyclononyne (BCN). The BCN group can bio-orthogonally react with azide-modified severe acute respiratory syndrome coronavirus-2 receptor-binding domain (SARS-CoV-2 RBD) trimer antigen to give the three-component Vaccine 1 . Notably, with a mere 3 mu g antigen, it elicited a balanced subclass of IgG titers and 20-fold more IgG2a than control vaccines, highlighting its potential for enhancing antibody-dependent cellular cytotoxicity. This strategy provides a practicable way to synthesize covalently linked dual immunostimulants. It expands the fully synthetic self-adjuvant protein vaccine that uses a single adjuvant to include two different types of adjuvants.

The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, 18F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC50 = 1.85-5.15 nM). After the radioisotope exchange labeling, [18F]L9 and [18F]L10 have PSMA specific cellular uptake (0.65 +/- 0.04% AD and 1.19 +/- 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMAtargeted aryl [18F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.

Dear Editor, Small cell lung cancer (SCLC) is a low-survival malignant lung cancer with mainly extensive stage (ES).1, 2 A major challenge in treating SCLC is chemotherapy resistance.3 However, studies on disease evolution and molecular mechanisms of resistance during chemotherapy are insufficient. Here, we conducted a multicentre, observational study to profile the multi-omics characteristics of tumour tissue, circulating tumour cell (CTC) and circulating tumour DNA (ctDNA) in Chinese ES-SCLC patients. This study enrolled 54 patients, including naïve cohort and relapsed cohort (Figure S1 and Table S1). Except for one patient who had distant metastasis in relapsed cohort, all the patients had ES-SCLC. According to the different stratification parameters, patients were divided by two manners. One manner was chemo-resistant vs chemo-sensitive, according to whether the time from the end of first-line therapy to disease progression exceeded 90 days (chemotherapy-free interval); other manner was responders vs non-responders, according to Response Evaluation Criteria in Solid Tumours (version 1.1), and the patient whose lesions shrank over 30% was defined as responder. The median overall survival (OS) and progression-free survival (PFS) for all patients were 9.6 m (95% confidence interval [CI]: 7.5‒12.2 m) and 4.5 m (95% CI: 3.4‒5.7 m), respectively. No clinical parameters had a significant effect on prognosis (Table S2). Chemo-sensitive/response patients had longer PFS (Figure S2), which suggested that different biological contexts may exist. The detection of ctDNA mutations was highly consistent with tumour results and the tumour mutation burden (TMB) was highly correlated (Figure S3A‒D and Tables S3 and S4), which indicated that ctDNA mutations could be used to monitor mutational changes during treatment with high confidence. As expected, TP53 and RB1 mutations were detected in most patients' baseline ctDNA (Figure S3A). Some frequently deleted genomic regions in tumours and more in CTCs were found (Figure S3E,F), which may indicate the evolution of genomic heterogeneity among diverse clones and the initial development of drug resistance. The tumour showed a high proportion of C > A transitions (Figure S3G). In both non-responders and chemo-resistant in baseline ctDNA, only the KDR gene (vascular endothelial growth factor receptor [VEGFR]) had a significantly higher mutation frequency (Figure 1A,C). The baseline ctDNA of chemo-resistant showed more significant deletion frequency, but only SORCS1 had a significant deletion frequency in baseline tumours (Figure S4). The TMB of baseline ctDNA in non-responders and microsatellite instability (MSI) score of baseline tumours in chemo-resistant were significantly higher (Figures 1B,D and S7B). However, other genomic indexes in tumour had no significant differences (Figures S5‒S7). Three pathways were highly enriched and one pathway was lower in non-responders (Figure S8). Tumour samples clustered into high and low levels of immune infiltrate by RNA-sequencing (Figure 2A,B). Although immune infiltration had no significant difference (Figure 2C,D), some immune populations in non-responders/chemo-resistant were significantly higher (Figures 2E, S9 and S10). The KRAS signalling pathways were enriched in non-responders in tumour (Figures 2F and S11), which were reported to affect the presence and suppressive function of tumouricidal cells.4 Conversely, several pathways related to proliferation and immunity were significantly up-regulated in responders/chemo-sensitive in both baseline tumours and CTCs (Figures 2F‒I, S11 and S12), suggesting that a more vital ability of differentiation and immunogenicity may occur in chemotherapy-sensitive tumour. The cell death pathway related to pyroptosis was different in baseline CTCs, and there was a significantly higher score of alkaliptosis in relapse nodes (Figure 2J,K). After chemotherapy, the CTCs in chemo-sensitive were significantly reduced at C3D1 while fewer changes were observed in chemo-resistant (Figure S13). The changes in the CTC counts and molecular tumour burden index (mTBI)5 were nearly consistent during conventional follow-up. The responders mostly tended to show a decreasing trend, while chemo-resistant showed a more frequent increasing trend (Figure S14). Phylogenetic relation trees showed a sustained high cancer cell fraction of major clones in chemo-resistant in both baseline and relapsed samples, but chemo-sensitive was characterised by the weakening of major clones in baseline samples (Figure S15A,B). Although the average number of mutations of trunk private clones was significantly higher in non-responders, the fraction of functional genes was lower (Figure S15C,D). The genomic landscape of 21 paired baseline and relapsed ctDNA showed no significant differences in TMB and mTBI (Figure S16). The KDR gene was still one of the top 10 frequently mutated genes (Figure 3A). The platinum drug resistance pathway was significantly enriched in baseline subclonal mutations and relapsed clonal mutations (Figure 3B), which indicated that tumour with drug-resistant mutations expanded from subclone to clone. Meanwhile, the tyrosine kinase inhibitor resistance and immune-related pathways were enriched in relapsed clonal mutations and subclonal mutations, respectively. Finally, we summarised the correlation between mutation/pathway/immunity and pathological response or chemotherapy sensitivity (Figure 3C), which may provide a comprehensive concept of treatment response and resistance mechanisms in SCLC. Consistent global copy number variation (CNV) results from cell lines and patient 1022 were observed, and some significant CNV changes were found between patients with or without durable clinical benefit (Figure S17). Patients with KDR mutation tended to have higher KDR expression levels and poor prognosis (Figure S18A,B). By using other datasets, we found that KDR was significantly highly expressed in SCLC-I and patients with low expression of the KDR were enriched in SCLC-A in the IMpower133 cohort6 (Figure S18C‒F). OS was significantly shorter in patients with high expression of KDR and VEGF pathways (Figure 4A,B). Moreover, the tumour with a high expression of KDR tended to be 'hot' (Figures 4C,D and S19). These findings were consistent with previous pathway enrichment results, suggesting that patients with KDR mutation and/or high expression of KDR may resist chemotherapy but benefit from immunotherapy, anti-folates and AURK inhibitors.7 Several chemotherapy agents contained higher IC50 in the high KDR expression group (Figure 4E), which may reveal a resistant trend. In conclusion, chemo-sensitive/response patients showed beneficial survival, and we found the potential mechanism was that KDR mutation, PI3K amplification, VEGF and KRAS pathways activation contribute to the development of chemotherapy resistance. These results provide critical information for the clinical decision of VEGF signalling pathway inhibitors combined with chemotherapy and imply that targeted therapies may benefit some patients who are resistant to chemotherapy. Besides, the difference in tumour microenvironment and several immune pathways enrichment between chemo-sensitive and chemo-resistant was consistent with the concept that tumours can take control of environment to reset the body homeostasis.8 However, we still lack sufficient evidence to determine the most appropriate therapies for recurring patients. Future studies are warranted on larger cohorts of patients in a real-world cohort to explore. Conceptualisation, supervision, funding acquisition and writing—review and editing: Ying Cheng. Resources, data curation, software, formal analysis, methodology, writing—original draft and writing—review and editing: Xuan Gao and Zelong Xu. Formal analysis, methodology and writing—review and editing: Bingfa Yan. Conceptualisation, resources and writing—review and editing: Jie Hu. Resources, data curation and writing—review and editing: Ying Liu, Jing Zhu, Ying Wang, Junfeng Wang, Changliang Yang, Hongxia Cui, Yanrong Wang, Guang Yang, Jie Hao, Peidong Li, Liang Zhang, Zili Li, Hongyu Wang, Yanli Sun, Shubo Zuo and Tianying Du. Software, formal analysis and writing—review and editing: Zhentian Liu, Xuefeng Xia and Xin Yi. Resources and writing—review and editing: Ying Xin, Ke Zheng, Yawen Yang and Kai Niu. Formal analysis and writing—review and editing: Jinhua Xu, Gan Zhang, Fei Chen and Ning Ding. We are greatly thankful for the funding for this study provided by the Development and Reform Commission of Jilin Province (2021C043‑1) and the Science and Technology Planning Project of Jilin Province (YDZJ202202CXJD009). We greatly appreciate the patients and investigators who participated in this study for providing the data. Xuan Gao, Bingfa Yan, Zelong Xu, Zhentian Liu, Xuefeng Xia and Xin Yi are employees of Beijing GenePlus Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. All patients provided written informed consent to conduct research in this study, and ethical approvals were obtained from the two hospitals (NOPRODLUC0001). The study received approval to conduct genomic research from the China Human Genetic Resources Administration Office (HGRAO, 2016-161). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Adjuvants enhance the body's immune response to a vaccine, often leading to better protection against diseases. Monophosphoryl lipid A analogues (MPLA, TLR4 agonists), α-galactosylceramide analogues (NKT cell agonists), and imidazoquinoline compounds (TLR7/8 agonists) are emerging novel adjuvants on market or under clinical trials. Despite significant interest in these adjuvants, a direct comparison of their adjuvant activities remains unexplored. We initially assessed the activities of various adjuvants from three distinct categories using the SARS-CoV-2 RBD trimer antigen. TLR4 and TLR7/8 agonists are discovered to elicit robust IgG2a/2b antibodies, which is crucial for eliciting antibody dependent cytotoxicity. While α-galactosylceramide analogs induced mainly IgG1 antibody. Then, because of the flexibility of the TLR7/8 agonist, we designed and synthesized a tri-component self-adjuvanting SARS-CoV-2 RBD vaccine, featuring a covalent TLR7 agonist and targeting mannoside. Animal studies indicated that this vaccine generated antigen-specific humoral immunity. Yet, its immunogenicity seems compromised, indicating the complexity of the vaccine.

sTF (sialyl-Thomsen-Friedenreich) is a type of tumor -associated carbohydrate antigens (TACAs) and is highly expressed in various human malignancies. To validate if sTF could be a valuable molecular target for future cancer vaccine development, in this work the sTF antigen was prepared by adopting a strategy combining chemical and enzymatic methods, and then was covalently conjugated to a carrier protein, CRM197. The preliminary immunological evaluation, performed on BALB/c mice, revealed that the sTF-CRM197 conjugate elicited high titers of specific IgG antibodies. FACS experiments showed that the antisera induced by sTF-CRM197 conjugate could specifically recognize and bind to sTF-positive cancer cells T -47D. Furthermore, the conjugate mediated effective and specific antibody -mediated complement -dependent cytotoxicity (CDC).

Optogenetic manipulation with single-cell resolution can be achieved by two-photon excitation; however, this frequently requires relatively high laser powers or holographic illumination. Here we developed a practical strategy to improve the efficiency of two-photon stimulation by positioning fluorescent proteins or small fluorescent molecules with high two-photon cross-sections in the vicinity of opsins. This generates a highly localized source of endogenous single-photon illumination that can be tailored to match the optimal opsin absorbance. Through neuronal and vascular stimulation in the live mouse brain, we demonstrate the utility of this technique to achieve more efficient opsin stimulation, without loss of cellular resolution. We also provide a theoretical framework for understanding the potential advantages and constrains of this methodology, with suggestions for future improvements. Altogether, this fluorescence transfer illumination method allows experiments difficult to implement in the live brain such as all-optical neural interrogation and control of regional cerebral blood flow.

Fluorinationof carbohydrates has been one of the strategies toincrease their enzymatic and chemical stabilities and reduce theirhydrophilicities, making this modification attractive for drug discoverypurposes. The synthesis of monofluorinated carbohydrates was achievedunder mild conditions by using SO2F2 as thedeoxyfluorination reagent in the presence of a base without extrafluoride additives. This method features low toxicity, easy availability,low cost, and high efficiency and can be subjected to diverse sugarunits.

Porous organic polymers (POPs), which feature high surface areas, robust skeletons, tunable pores, adjustable functionality and versatile applicability, have constituted a designable platform to develop advanced organic materials. Endowing polyelectrolytes with the distinct characteristics of POPs will attract mounting interest as the structural diversity of polyelectrolytes will bring the new hope of intriguing applications and potential benefits. In this review, the striking progress in ionized POPs (i-POPs) has been systematically summarized with regard to their synthetic strategies and applications. In the synthesis of i-POPs, we illustrate the representative ionic building blocks and charged functional groups capable of constructing the polyelectrolyte frameworks. The synthetic methods, including direct synthesis and post-modification, are detailed for the i-POPs with amorphous or crystalline structures, respectively. Subsequently, we outline the distinctive performances of i-POPs in adsorption, separation, catalysis, sensing, ion conduction and biomedical applications. The survey concerns the interplay between the surface chemistry, ionic interaction and pore confinement that cooperatively promote the performance of i-POPs. Finally, we conclude with the remaining challenges and promising opportunities for the on-going development of i-POPs.

The anomeric configuration can greatly affect the biological functions and activities of carbohydrates. Herein, we report that N-phenyltrifluoroacetimidoyl (PTFAI), a well-known leaving group for catalytic glycosylation, can act as a stereodirecting group for the challenging 1,2-cis α-glycosylation. Utilizing rapidly accessible 1,6-di-OPTFAI glycosyl donors, TMSOTf-catalyzed glycosylation occurred with excellent α-selectivity and broad substrate scope, and the remaining 6-OPTFAI group can be cleaved chemoselectively. The remote participation of 6-OPTFAI is supported by the first characterization of the crucial 1,6-bridged bicyclic oxazepinium ion intermediates by low-temperature NMR spectroscopy. These cations were found to be relatively stable and mainly responsible for the present stereoselectivities. Further application is highlighted in glycosylation reactions toward trisaccharide heparins as well as the convergent synthesis of chacotriose derivatives using a bulky 2,4-di-O-glycosylated donor.

Around 100 Streptococcus pneumonia (Spn) serotypes have been discovered, 90% of the severe diseases in children are caused by 13 serotypes. With the success of pneumococcal bacterial polysaccharide conjugate vaccines (PCVs), the burden of pneumococcal disease has been significantly reduced. Serotype 31 is a non-vaccine serotype and has increased in prevalence. By using Nuclear Magnetic Resonance (NMR) as the primary tool, we report the revised serotype 31 polysaccharide (s-31-ps) structure as [→3)-β-D-Galf-(5/6-OAc)-(1 → 3)-β-D-Galp-(1 → 3)-β-L-Rhap-(2-OAc)-(1 → 2)-α-L-Rhap-(1 → 4)-β-D-GlcpA-(1→]n. Furthermore, the reductive amination-conjugate of serotype 31 polysaccharide and cross reacting material (CRM197) protein was prepared in organic solvent (N,N-dimethylformamide, DMF) instead of water. The reaction is faster, and the DMF conjugate elicited comparable immune responses with the aqueous conjugate. S-31-ps conjugate vaccine has the potential of being included in the next-generation PCV vaccines.