CARBOHYDRATE POLYMERS
·
2016
·
IF 4.219
Feifei Sun,Hong Niu,Dongdong Wang,Yuanyuan Wu,Haibo Mu,Lili Ma,Jinyou Duan
Current studies have revealed the excellent moisture absorption-retention capacity of hyaluronan (HA); however, HA is easily degraded by hyaluronidase on the surface of skin. So, it is very necessary to develop an alternative derivative with low cytotoxicity and resistance to hyaluronidase. Herein, a HA decorated with photocaged groups was synthesized. The moisture absorption-retention capacity and hyaluronidase resistance of photocaged HA (HA-DMNB) and products of HA-DMNB irradiated by ultraviolet for different time (IHA-DMNB), were investigated. Results show that HA-DMNB is more resistant to hyaluronidase than HA, and HA-DMNB could release free carboxyl groups of HA upon ultraviolet to bond with H 2 O. More importantly, HA-DMNB was protective against UV light. In addition, HA-DMNB and IHA-DMNB were observed to be nontoxic to HaCat cells. This study indicates that HA-DMNB may be effectively used as a moisture-preserving reagent.
研究领域:
生物化学
·
皮肤科学
·
材料科学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 6
·1645
·
IF 5.4
Zhe Zhang,Zuyi Chen,Cheng Li,Zhenyu Xiao,Yuan Luo,Xiaochen Pan,Liang Xu,Xuesong Feng
Antisense oligonucleotides (ASONs) have proven potential for the treatment of various diseases. However, their limited bioavailability restricts their clinical application. New structures with improved enzyme resistance stability and efficient drug delivery are needed. In this work, we propose a novel category of ASONs bearing anisamide conjugation at phosphorothioate sites for oncotherapy. ASONs can be conjugated with the ligand anisamide very efficiently and flexibly in a solution. The conjugation sites and the ligand amount both influence anti-enzymatic stability and cellular uptake, resulting in changes in antitumor activity that are detectable by cytotoxicity assay. The conjugate with double anisamide (T6) was identified as the optimal conjugate, and its antitumor activity and the underlying mechanism were examined further in vitro and in vivo. This paper presents a new strategy for the design of nucleic acid-based therapeutics with improved drug delivery and biophysical and biological efficacy.Keywords:oligonucleotide conjugation;anisamide;anti-enzymatic stability;cellular uptake;antitumor activity
研究领域:
药学
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2018
·
IF 4.244
Junqing He,Junyan Wang,Nan Zhang,Luyao Shen,Linlin Wang,Xiao Xiao,Yan Wang,Tao Bing,Xiangjun Liu,Songqing Li,Dihua Shangguan
Ovarian cancer is regarded as the most lethal gynecologic malignancy with poor prognosis and high mortality rate. Drug-resistance was thought to be the main obstacle to improving overall survival rate of ovarian cancer. New ligands for drug-resistant ovarian cancer cells have potential for the development of diagnosis and therapy of ovarian cancer. In present work, we reported two aptamers , HF3–58 and HA5–68 generated by cell-SELEX, against a paclitaxel-resistant ovarian cancer cell line (A2780T). Both two aptamers exhibited high selectivity and strong affinity to target cells with low nanomolar dissociation constants . The binding of aptamers to target cells was independent of divalent ions, and was tolerant of incubation temperature and nucleases in serum. Molecular targets of the two aptamers were preliminarily demonstrated to be two different glycoproteins on cell surface of A2780T cells. Owing to the structure stability and high resistance to nuclease, these two aptamers had good performance in the detection of drug-resistant ovarian cancer cells in human serum.
研究领域:
癌症生物学
·
分子生物学
·
药学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Yating Li,Jason Tan,Yanqin Tu,Jingnan Wu,Zaifang Zhang,Yifeng Wei,Xinan Jiao,Yan Zhou
DNA base modification is a common strategy used by bacteriophages to evade host immune detection. A prominent example is dU-DNA, where thymidine is globally replaced with 2′-deoxyuridine. Despite its widespread occurrence, dU-DNA's biosynthetic pathways and functional roles remain incompletely understood. Here, different enzymes supporting dU-DNA biosynthesis in phage PBS1, Roseophage DSS3_VP1, and Yersiniophage PhiR1-37 are identified and characterized. The dU nucleotide precursor is supplied by phage dCTP deaminases (Dcds). Thymidine nucleotides are degraded by dTMP phosphatases (Dtms) in PBS1 and DSS3_VP1, and by a dTTP pyrophosphatase (Dtt) in PhiR1-37, preventing incorporation into phage DNA. The dU-DNA, isolated from Yersiniophage PhiR1-37 or synthesized by PCR, demonstrates resistance to cleavage by restriction enzymes recognizing thymidine-containing sequences, partial resistance to Lb Cas12a nuclease recognizing a TTTV PAM site, while remaining sensitive to Sp Cas9 nuclease recognizing a NGG PAM site. A phylogenetic analysis of PBS1 dCTP deaminase and closely related T4 phage dCMP deaminase suggest possible evolutionary origins from bacterial dCDP deaminases. Overall, these findings suggest independent acquisition of dU-DNA biosynthetic enzymes and pathways in the diverse phages, and support its protective function against different host-encoded nucleases.
研究领域:
分子生物学
·
病毒学
·
微生物学
·
基因工程
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核酸代谢
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免疫逃避
·
进化生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Weikang Yu,Yu Sun,Wenyu Li,Xu Guo,Xuesheng Liu,Wanpeng Wu,Wanqi Yu,Jiajun Wang,Anshan Shan
Targeting the limitation of antimicrobial peptides (AMPs) application in vivo, self-assembled AMPs library with specific nanostructures is expected to gradually overtake monomer AMPs libraries in the future. Peptide polymers are fascinating self-assembling nanoscale structures that have great advantage in biomedical applications because of their satisfactory biocompatibility and versatile properties. Herein, we describe a strategy for inducing the self-assembly of T9W into nanostructured antimicrobial micelles with evidently improved pharmacological properties, that is, PEGylation at the C-terminal of T9W (CT9W1000), an antibacterial biomaterial that self-assembles in aqueous media without exogenous excipients, has been developed. Compared with parental molecular, the CT9W1000 is more effective against Pseudomonas aeruginosa, and its antibacterial spectrum had also been broadened. Additionally, CT9W1000 micelles had higher stability under salt ion, serum, and acid–base environments. Importantly, the self-assembled structure is highly resistant to trypsin degradation, probably allowing T9W to be applied in clinical settings in the future. Mechanistically, by acting on membranes and through supplementary bactericidal mechanisms, CT9W1000 micelles contribute to the antibacterial process. Collectively, CT9W1000 micelles exhibited good biocompatibility in vitro and in vivo, resulting in highly effective treatment in a mouse acute lung injury model induced by P. aeruginosa PAO1 without drug resistance. These advances may profoundly accelerate the clinical transformation of T9W and promote the development of a combination of peptide-based antibiotics and PEGylated nanotechnology.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
微生物学
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DOI
PubMed
高影响因子
Current Protocols
·
2023
·Vol. 3
·期 11
·e923
·
IF 0
Xuan Chen,Long Xie,Chenglong Zhang,Shen Tian,Zeyu Tang,Weiwei Tian,Patrick Lu,Xianbin Yang
Although small interfering RNA (siRNA) is a key player among gene inhibition therapeutics, there are many obstacles to the development of siRNA drugs due to inherent properties of oligonucleotides, including the unsatisfactory stability of unmodified siRNA, poor pharmacokinetic distribution, and the toxicity induced by off-target effects. To maximize treatment potency, chemical modification of siRNA has undoubtedly been the most successful strategy by far. Widely applied modifications include phosphorothioate linkages, 2′- O -methyl modifications, and 2′-fluoro modifications, among others. To extend the family of chemical modifications for oligonucleotides, 2′- O -cyanoethylated RNA analogs were developed through the replacement of the 2′-hydroxyl group with a 2′- O -cyanoethyl group (-OCH 2 CH 2 CN). This modification can provide several advantages over unmodified RNA, such as increased stability, improved binding affinity to complementary DNA or RNA strands, and resistance to degradation by cellular nucleases. The 2′- O -cyanoethyl-modified RNAs not only are applied in RNA silencing machinery but also act as research tools for studying RNA structure and function or for developing RNA-based diagnostics. Therefore, the efficient synthesis, deprotection, purification, and characterization of 2′- O -cyanoethylated RNAs deserves more attention. This protocol describes the chemical synthesis of 2′- O -cyanoethylated nucleotides and the solid-phase synthesis, deprotection, and purification of 2′- O -cyanoethylated RNAs. © 2023 Wiley Periodicals LLC. Basic Protocol 1 : Preparation of 6- N -dimethylformamidyl-5′- O -dimethoxytrityl-2′- O -cyanoethyl adenosine 3′-(2-cyanoethyl N , N -diisopropyl)phosphoramidite Basic Protocol 2 : Preparation of 4- N -acetyl-5′- O -dimethoxytrityl-2′- O -cyanoethyl cytidine 3′-(2-cyanoethyl N , N -diisopropyl)phosphoramidite Basic Protocol 3 : Preparation of 2- N -dimethylformamidyl-5′- O -dimethoxytrityl-2′- O -cyanoethyl guanine 3′-(2-cyanoethyl N , N -diisopropyl)phosphoramidite Basic Protocol 4 : Preparation of 5′- O -dimethoxytrityl-2′- O -2-cyanoethyl uridine 3′-(2-cyanoethyl N , N -diisopropyl)phosphoramidite Basic Protocol 5 : Solid-phase synthesis of 2′- O -cyanoethylated RNA analogs Basic Protocol 6 : Deprotection and purification of synthesized 2′- O -cyanoethyl-RNAs
研究领域:
分子生物学
·
生物化学
·
药物化学
·
RNA治疗学
·
有机合成
✓ 已验证
DOI
iScience
·
2024
·
IF 4.6
Ming-Xin Cao,Zhan-Yin Qian,Yan-Jie Liang,Qi-Yao Liu,Han-Ping Wang,Yang Meng,Yin-Song Wang,Yue Wang
Dental caries is a common disease resulting from tooth demineralization caused by bacterial plaque. Probiotics have shown great potential against caries by regulating the balance of oral flora. However, obstacles such as poor colonization and lysozyme sensitivity in oral cavity hinder their further application. In this study, an efficient layer-by-layer surface coating of tannic acid (TA)-Ca 2+ and casein phosphopeptide (CPP) was applied to the probiotic Bifidobacterium infantis (BI) with potential anti-caries activity. Multi-functionalized probiotics thus prepared (called BI@TA-Ca 2+ @CPP) exhibited similar growth pattern, resistance to lysozyme and enhanced colonization potential. The ability of BI@TA-Ca 2+ @CPP in inhibiting cariogenic biofilm formation was improved. Moreover, BI@TA-Ca 2+ @CPP showed excellent remineralization efficacy. In a caries-induced rat model, BI@TA-Ca 2+ @CPP significantly prevented the occurrence and progression of tooth decay, meanwhile showing good biocompatibility. In summary, this study underlines the importance of probiotics coating in antibiofilm and remineralization activity as a promising strategy against dental caries.
研究领域:
龋齿预防
·
口腔微生物学
·
益生菌工程
·
生物矿化
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产品关联
DOI
PubMed
高影响因子
Current Protocols
·
2024
·Vol. 4
·期 1
·e956
·
IF 0
Xuan Chen,Long Xie,Chenglong Zhang,Shen Tian,Zeyu Tang,Ming Xiang,Weiwei Tian,Patrick Lu,Xianbin Yang
The integration of fluorine atoms into biologically active organic compounds has proved to be a vital technique in small molecule drugs. This technique can substantially enhance crucial properties, including metabolic stability, lipophilicity, and bioavailability, often with a mere addition of a single fluorine atom or a trifluoromethyl group. Over the past few decades, this concept has also been applied in nucleic acid chemistry. A commonly employed 2′-OH substitution is the introduction of a 2′-deoxy-2′-fluoro (2′-F) group. The strong electronegativity of fluorine prompts the modified siRNA to readily adopt a C3′- endo conformation, resulting in significant advantages in terms of binding affinity. To enrich the toolbox of chemical modification of oligonucleotides, the replacement of the 2′-OH with the 2′- O -trifluoromethyl group has been developed in RNA analog synthesis. Oligodeoxynucleotides containing the 2′- O -trifluoromethyl group can greatly increase the thermal stability of DNA/RNA duplexes depending on the position and amount of the modification. Moreover, 2′- O -trifluoromethylated oligodeoxynucleotide also exhibited a slightly higher resistance to snake venom phosphodiesterase than the unmodified oligodeoxynucleotide. The 2′- O -trifluoromethylated oligonucleotides can emerge as a label to study RNA structure and function as well, or to develop DNA/RNA-based diagnostics. Hence, it is necessary to report an effective method for the synthesis, deprotection, purification, and characterization of oligonucleotides bearing a 2′ -O -trifluoromethyl group. © 2024 Wiley Periodicals LLC. Basic Protocol 1 : Preparation of 6- N -benzoyl-5′- O -dimethoxytrityl-2′- O -trifluoromethyl adenosine 3′-(2-cyanoethyl N,N -diisopropyl)phosphoramidite Basic Protocol 2 : Preparation of 4- N -acetyl-5′- O -dimethoxytrityl-2′- O -trifluoromethyl cytidine 3′-(2-cyanoethyl N,N -diisopropyl)phosphoramidite Basic Protocol 3 : Preparation of 2- N -isobutyryl-5′- O -dimethoxytrityl-2′- O -trifluoromethyl guanine 3′-(2-cyanoethyl N,N -diisopropyl)phosphoramidite Basic Protocol 4 : Preparation of 5′- O -dimethoxytrityl-2′- O -2-trifluoromethyl uridine 3′-(2-cyanoethyl N,N -diisopropyl) phosphoramidite Basic Protocol 5 : Solid-phase synthesis of 2′- O -trifluoromethylated RNA analogs Basic Protocol 6 : Deprotection and purification of 2′- O -trifluoromethyl-RNAs
研究领域:
生物有机化学
·
核酸化学
·
药物化学
·
RNA生物学
·
分子生物学
·
药学
✓ 已验证
DOI
ACS Applied Materials & Interfaces
·
2015
·
IF 6.723
Feng Liu,Yuecheng Cui,Lei Wang,Hongwei Wang,Yuqi Yuan,Jingjing Pan,Hong Chen,Lin Yuan
It is important to effectively maintain and modulate the bioactivity of protein-nanoparticle conjugates for their further and intensive applications. The strategies of controlling protein activity via “tailor-made surfaces” still have some limitations, such as the difficulties in further modulation of the bioactivity and the proteolysis by some proteases. Thus, it is essential to establish a responsive protein-nanoparticle conjugate system to realize not only controllable modulations of protein activity in the conjugates by incorporating sensitivity to environmental cues but also high resistance to proteases. In the work reported here, Escherichia coli (E. coli) inorganic pyrophosphatase (PPase) and poly(N-isopropylacrylamide) (pNIPAM) were both fabricated onto gold nanoparticles (AuNPs), forming AuNP-PPase-pNIPAM conjugates. The bioactivity-modulating capability of the conjugates with changes in temperature was systematically investigated by varying the molecular weight of pNIPAM, the PPase/pNIPAM molar ratio on AuNP, and the orientation of the proteins. Under proper conditions, the activity of the conjugate at 45 °C was approximately 270% of that at 25 °C. In the presence of trypsin digestion, much less conjugate activity than protein activity was lost. These findings indicate that the fabrication of AuNP-protein-pNIPAM conjugates can both modulate protein activity on a large scale and show much higher resistance to protease digestion, exhibiting great potential in targeted delivery, controllable biocatalysis, and molecular/cellular recognition.
研究领域:
纳米生物技术
·
生物化学
·
材料科学
·
生物催化
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Min Chen,Rui Han,Wenqi Wang,Yang Li,Xiliang Luo
A brief and universal ultralow fouling sensing platform capable of assaying targets in complex biofluids was developed based on designed antifouling peptides that could form a loop-closed structure with enhanced stability. The newly designed peptide with thiol groups in its two terminals self-assembled onto a gold nanoparticle (AuNP)-modified electrode surface to form a stable loop structure, which displayed excellent antifouling performance, outstanding stability under enzymatic hydrolysis, and satisfactory long-term antifouling capability in complex biofluids (clinical human serum). The antifouling and highly sensitive electrochemical aptasensor was constructed via one-step co-immobilization of the designed peptides and aptamers onto the electrode surface modified with electrodeposited poly(3,4-ethylenedioxythiophene) (PEDOT) and AuNPs. The developed peptide-based aptasensor exhibited a decent response for the analysis of the cancer antigen 125 (CA125), with a relatively wide linear range (0.1–1000 U mL–1) and a low limit of detection (0.027 U mL–1), and was capable of detecting CA125 in clinical serum samples with acceptable accuracy. This antifouling strategy-based self-assembled peptide with a loop-closed structure provided a potential path for the development of various low-fouling biosensors for application in complex biological fluids.
研究领域:
生物传感器
·
电化学
·
纳米技术
·
分析化学
·
生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Xichan He,Keyong Tang,Xiumin Li,Fang Wang,Jie Liu,Fangfang Zou,Mengyuan Yang,Meixuan Li
Inspired by the mechanism of bone formation, a porous collagen-carboxymethyl cellulose/hydroxyapatite (Col-CMC/HA) composite was designed and fabricated using a biomimetic template of Col and CMC protein-polysaccharide bi-molecules. The morphology, composition and physical properties of Col-CMC/HA composites were characterized systematically. It was found that the nano-HA homogenously distributed on the surface of Col-CMC bi-templates while the composite presented 3D porous structure with pore size from 100 μm to 300 μm. The porosities of composites were located at the range of 71%–85%. Besides, the compressive strength of composites was highly depended on the ratio of Col to CMC in the organic template. The optimized composite in respect to physical properties showed a compressive strength as high as 7.06 MPa, quite close to that of natural bone. The high relative growth rate of wild-type mouse embryonic fibroblasts cells was found for the composite, indicating a good biocompatibility. The organic-inorganic composite also behaved good in collagenase resistance and could be biodegraded in 8 weeks, with about 50% of initial weight left at the ratio of Col to CMC of 1:9. The results demonstrated that the Col-CMC/HA composite by bi-molecular template method was a rational and safe method to prepare biomaterials with tunable properties.
研究领域:
生物材料
·
组织工程
·
材料科学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
NATURE BIOTECHNOLOGY
·
2022
·Vol. 40
·期 11
·1601-1609
·
IF 68.164
Chen Ji,Chen Mengyin,Zhu Ting F.
Mirror-image aptamers made from chirally inverted nucleic acids are nuclease-resistant and exceptionally biostable, opening up opportunities for unique applications. However, the directed evolution and selection of mirror-image aptamers directly from large randomized l -DNA libraries has, to our knowledge, not been demonstrated previously. Here, we developed a ‘mirror-image selection’ scheme for the directed evolution and selection of biostable l -DNA aptamers with a mirror-image DNA polymerase. We performed iterative rounds of enrichment and mirror-image polymerase chain reaction (PCR) amplification of l -DNA sequences that bind native human thrombin, in conjunction with denaturing gradient gel electrophoresis (DGGE) to isolate individual aptamers and l -DNA sequencing-by-synthesis to determine their sequences. Based on the selected l -DNA aptamers, we designed biostable thrombin sensors and inhibitors, which remained functional in physiologically relevant nuclease-rich environments, even in the presence of human serum that rapidly degraded d -DNA aptamers. Mirror-image selection of biostable l -DNA aptamers directly from large randomized l -DNA libraries greatly expands the range of biomolecules that can be targeted, broadening their applications as biostable sensors, therapeutics and basic research tools.
研究领域:
分子生物学
·
生物技术
·
纳米技术
·
治疗学
·
传感器
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）