Relationship between immune regulation and structure of polysaccharides / 中国中药杂志

Polysaccharides have significant immunomodulatory activity and have good development value in food and medicine fields. At present, there are many studies on the chemical structure and immune activity of polysaccharides, but the relationship between them of polysaccharides has not been fully explained, which limits the further development and utilization of polysaccharide resources. The immune activity of polysaccharides is closely related to their own structure. This paper systematically summarized the relationship between the relative molecular weight, monosaccharide composition, glycosidic bond types, chemical modification, and advanced conformation of polysaccharides and the immune regulation, aiming to provide references for the profound study of polysaccharide structure-activity relationship and utilization of polysaccharides.

Research progress in antisense drug mechanism and chemical modification strategies / 药学学报

Over the past three decades, more and more antisense drugs have been approved for marketing or clinical trails. Antisense technology has become the focus of pharmaceutical research due to its unique advantages in treating diseases and strong clinical development potential. There is a big difference from traditional small molecule chemical drugs, and macromolecular protein biological drugs. Antisense drugs are a very independent drug form. Antisense drugs were initially used to treat diseases with single gene mutations, but recently they have gradually begun to be used for the treatment of common diseases. Rational antisense drug design is crucial for disease treatment based on genetics. This paper reviews the latest progress in the field of action mechanism, chemical modification and delivery strategy of antisense drugs, and analyzes the current intractable problems. It is believed that with the resolution of these problems, the research of antisense drugs can reach a new level.

Progress in clinical pharmacology of oligonucleotides / 药学学报

Following small molecules and monoclonal antibodies, oligonucleotides are expected to overcome the rare and refractory human diseases. It has been attracted the attention of the pharmaceutical industry since the approval of six oligonucleotides in recent years because of their unique mechanism of regulating disease gene transcription at the RNA level. As a new class of drug molecules, oligonucleotides are highly polar, charged, and need to be improved by means of chemical modification and drug delivery systems. And therefore, they have different clinical pharmacology properties compared with chemical molecules and monoclonal antibodies, which pose new challenges for early clinical development. This paper reviews the characteristics of oligonucleotides from the perspective of technological development, mechanism of action, human pharmacokinetics, efficacy and safety.

Biossorção de íons Cr(III) de soluções aquosas sintéticas e efluente de curtume utilizando a macrófita aquática Pistia stratiotes / Biosorption of Cr(III) ions from synthetic aqueous solutions and tannery effluent using the macrophyte Pistia stratiotes

RESUMO O cromo é um metal tóxico amplamente utilizado em processos industriais, por isso a constante preocupação com os efluentes líquidos gerados. Uma vez lançados sem o devido tratamento podem comprometer a qualidade do corpo receptor. Este trabalho teve por objetivo analisar o processo de biossorção na remoção de íons Cr(III) de soluções aquosas sintéticas e efluente de curtume utilizando como biossorvente a macrófita aquática Pistia stratiotes in natura (PN) e quimicamente modificada (PM) com hidróxido de sódio e ácido cítrico. Realizou-se o preparo, a caracterização dos biossorventes e os experimentos de biossorção. Os estudos de equilíbrio indicaram que a capacidade máxima de biossorção foi de 58,16 e 19,80 mg g-1 para PM e PN, respectivamente. Nos testes utilizando efluente bruto de curtume, a remoção de cromo foi de 28,26% para ambos os biossorventes, e no efluente da lagoa de tratamento biológico, a maior taxa de remoção do metal foi obtida pelo biossorvente PM, com 65,44%. Os resultados demonstraram que a utilização de P. stratiotes como biossorvente apresenta-se como uma alternativa eficaz e de baixo custo, porém estudos complementares são necessários a fim de avaliar sua aplicação em escala real.

ABSTRACT Chromium is a toxic metal widely used in industrial processes, so the concern with the liquid effluents generated is constant, that once released without proper treatment can compromise the quality of the receiver body. The study aimed at analyzing the process of biosorption in removing Cr(III) ions of synthetic aqueous solutions and tannery effluent using as biosorbent the Pistia stratiotes macrophyte in natura (PN) and chemically modified (PM) with sodium hydroxide and citric acid. The preparation, characterization of the biosorbents and the experiments of biosorption were performed. Equilibrium studies indicated that the maximum biosorption capacity for PM was 58.16 mg g-1 and 19.80 mg g-1 for PN. In the tests using raw effluent from tannery, chromium removal was 28.26% for both biosorbents, and in the effluent from biological treatment lagoon, the higher rate of metal removal was obtained by biosorbent PM with 65.44%. The results showed that the use of P. stratiotes as biosorbent may be an effective and low-cost alternative and that additional studies are needed to assess its full-scale application.

Application of methods on target identification and validation of label-free natural products / 药学学报

Natural products areone source of new drugs, and their target identification is pivotal forelucidating the mechanism of action. Most methods of target discovery and validation utilize labeling natural products with probes. This is time-consuming and laborious, and often results in activity decrease or change of the natural products. Recent methods withoutchemicalmodificationhave become the main force in the target identification of natural products, including direct or indirect methods. Direct methods are mainly based on the principle of affinity and stability of protein, and indirect methods infer the drug target from the change in physiological responses or biochemical signatures. This review summarizes recent methods for target identification and validation of label-freenatural products, providing new ideas and strategies for future research in natural products.

Research Progress in the Chemical Modification of Chitosan and the Antioxidant Activity of Its Derivatives / 中国药师

Chitosan (CS) is a natural,non-toxic biopolymer mainly made from the deacetylation of chitin. Chitosan has good bio-compatibility with unique antioxidant and biodegradable properties. Due to the poor solubility of chitosan in neutral or alkalinized media,the application of chitosan is restricted. Thus,numerous chitosan derivatives have been developed through chemical modifica-tions to broaden the application scope and improve its value. Chitosan and its derivatives with antioxidant activity have shown superior medical value in recent years. In this paper,several modification methods of chitosan were reviewed. In addition,the research progress in chitosan and its derivatives as antioxidants was introduced.

Terpene Esters from Natural Products: Synthesis and Evaluation of Cytotoxic Activity

ABSTRACT Natural steroids and triterpenes such as b-sitosterol, stigmasterol, lupeol, ursolic and betulinic acids were transformed into its hexanoic and oleic esters, to evaluate the influence of chemical modification towards the cytotoxic activities against tumor cells. The derivatives were evaluated against five tumor cell lines [OVCAR-8 (ovarian carcinoma); SF-295 (glioblastoma); HCT-116 (colon adenocarcinoma); HL-60 (leukemia); and PC-3 (prostate carcinoma)] and the results showed only betulinic acid hexyl ester exhibits cytotoxic potential activity.

Synthesis and antisense properties of 2'β-F-/2'α-F-2'-deoxy-uridines modified oligonucleotides with 4'-C-(2-methoxyethoxy) substituent / 药学学报

Chemical modification is critical for the therapeutic applications of antisense oligonucleotides. Novel 4'-C-MOE and 2'-fluoro-modified monomer 2'-F-4'-C-MOE-araU and its epimeric 2'-F-4'-C-MOE-rU were synthesized from 2'-fluorinated arabinourine (2'-F-araU) and 2'-fluorouridine (2'-F-rU), respectively. Their phosphoramidites were synthesized and successfully incorporated into oligodeoxynucleotides. The mismatch discrimination ability of these unnatural monomers and their effect on thermal stability were evaluated in the context of dsDNA and DNA-RNA chimeras. The thermal denaturation studies showed that the incorporation of 2'-F-4'-C-MOE-araU led to enhanced binding affinity to complementary RNA strand and almost equivalent binding ability to complementary DNA, when compared with 2'-F-4'-C-MOE-rU and 2'-F-araU modified duplexes.Especially a C-H…F-C pseudohydrogen bond was supposed to contribute more binding affinity at uridine-purine steps, meanwhile, 2'-F-4'-C-MOE-araU had almost the same base discriminatory ability as uridine in dsDNA and DNA-RNA chimeras, while 2'-F-4'-C-MOE-rU was found to have only moderate RNA hybridization ability. However, 2'-F-4'-C-MOE-araU at 3'-end of oligonucleotide could not led to more nuclease hydrolytic stability than that with 2'-F-4'-C-MOE-rU modification. These results demonstrated the feasibility of C4'-MOE modification on 2'-F-ANA and the dramatic effects of the 2'-F substituent, which provides a new approach fo r further chemical modification of antisense drugs.

Biomanufactured polyhydroxyalkanoates (PHA) modification: a review / 生物工程学报

In this review, we presented the industrial status of biomanufactured polyhydroxyalkanoates (PHA), including poly (3-hydroxybutyrate) (PHB), poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly (3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB)), and poly (3-hydroxybutyrate-3-hydroxycaproate) (PHBH). A lot of modification studies, aimed at solving problems of poor thermal stability, narrow processing window and other drawbacks of PHA, are discussed. The properties of PHA can be optimized by using proper modification method, in order to expand its applications.

Chemical Modifications of Peptides and Proteins with Low Concentration Formaldehyde Studied by Mass Spectrometry / 分析化学

Abstract Formaldehyde has been widely employed to immobilize clinical tissue specimens, inactivate toxins and viruses in biomedical fields. Formaldehyde can react with active groups in bio-molecules such as proteins, resulting in protein cross-linking, inactivation, and immobilization. By using several standard peptides and tryptic peptides from matrix protein of influenza virus as experimental models, we studied the chemical modifications of peptides and proteins with formaldehyde by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and nano-electrospray quadruple time-of-flight tandem mass spectrometry. The reaction between formaldehyde and peptides was performed under the same conditions as those during inactivation of virus (4℃, 0. 025% Formalin (V/V), 37% formaldehyde solution (w/w), and 72 h). The results indicated that under above conditions, formaldehyde could react with amino group of N-terminus of standard peptide to generate a methylol adduct, which was further condensed into an imine to generate+12 Da product. Besides, formaldehyde could react with side chain of two amino acids such as arginine and lysine, yielding +12 Da product respectively. The analysis of the reaction between formaldehyde and tryptic peptides from matrix protein of influenza virus showed that +24 Da products could be detected in most peptides due to combinational contribution from N-terminus of peptide (+12 Da ) and side chain of C-terminal arginine or lysine (+12 Da) . Moreover, a +36 Da product was detected for a peptide with miss-cut site. The results indicated that low-concentration formaldehyde primarily reacted with amino group on N-termini of peptides and proteins, as well as the side chains of arginine and lysine residues. The present study suggested an effective mass spectrometry-based method for analyzing the reaction between low-concentration formaldehyde and peptides and proteins, thus provided strategies for interpretation for the mass spectra of reaction products.

Active derivatives based on the resveratrol scaffold: Research advances / 国际药学研究杂志

Natural product resveratrol has antioxidation, cardiovascular protection and many other useful biological activities. In recent years, many researchers have paid more and more attention to it. However it cannot be used as candidate for the development of new drug due to its poor druggability. Novel resveratrol derivates with improved water solubility and highly potent biological activity could be obtained by chemical modifying of chemical structure of resveratrol. Researches have shown that resveratrol derivatives exhibit many kinds of attractive activities, including antitumor, reducing blood fat, antiviral, anti-neurodegenerative diseases and so on, which makes them could be used as leads for the further developing of new drugs. This review discusses the development of novel resveratrol derivatives by chemical modification in recent years.

Active derivatives based on the resveratrol scaffold:research advances / 国际药学研究杂志

Natural product resveratrol has antioxidation,cardiovascular protection and many other useful biological activities. In recent years,many researchers have paid more and more attention to it. However it cannot be used as candidate for the development of new drug due to its poor druggability. Novel resveratrol derivates with improved water solubility and highly potent biological activity could be obtained by chemical modifying of chemical structure of resveratrol. Researches have shown that resveratrol derivatives exhib?it many kinds of attractive activities,including antitumor,reducing blood fat,antiviral,anti-neurodegenerative diseases and so on, which makes them could be used as leads for the further developing of new drugs. This review discusses the development of novel resve?ratrol derivatives by chemical modification in recent years..

Effect of covalent attachment of neomycin on conformational and aggregation properties of catalase.

The carboxylic groups of glutamic acid and aspartic acid residues of catalase (CAT) were chemically modified using the treatment of the enzyme with 1-ethyl-3-(3'-dimethylamino) carbodiimide hydrochloride (EDC) and neomycin. The effect of covalent attachment of neomycin on the enzymatic activity, conformational and aggregation properties of CAT was investigated. The modification of CAT with different concentrations of neomycin showed two different types of behavior, depending up on the concentration range of neomycin. In the concentration range from 0.0 to 5.2 mM, neomycin-modified CAT, compared to the native enzyme exhibited higher α-helix content, reduced surface hydrophobicity, little enhancement in CAT activity and a better protection against thermal aggregation, whereas at concentrations greater than 5.2 mM, the modified enzyme exhibited a significant decrease in CAT activity and an increase in random coil content which may result in disorder in the protein structure and increase in thermal aggregation. This modification is a rapid and simple approach to investigate the role of aspartate and glutamate residues in the structure, function and folding of CAT.

Preparation and characterization of superoxide dismutase chemically modified by 6-O-quaternized chitosan / 中国药学杂志

OBJECTIVE: To chemically modify superoxide dismutase (SOD) with 6-O-quaternized chitosan. METHODS: 2, 3- Epoxypropyl trimethyl ammonium chloride was grafted to reactive C6-OH of chitosan to obtain O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC). O-HTCC was covalently coupled to SOD via EDC/NHS-mediated reaction, followed by purification on DEAE Sepharose fast flow column. The conjugates were analyzed by SDS-PAGE, HPLC, and circular dichroism. The enzyme activity of the conjugates was determined using pyrogallol autoxidation assay. RESULTS: SOD was successfully modified by O-HTCC at an efficiency of 90%. The homogeneous conjugates showed similar secondary structure and retained 81.1% of enzyme activity compared with native SOD. CONCLUSION: SOD can be efficiently modified by O-HTCC to prepare O-HTCC-SOD conjugates with high activity retention rate.

Physical and chemical properties of acetylated low molecular weight heparin and its antineoplastic effect in vitro / 中国药理学通报

Aims To synthesize acetylated low molecu-lar weight heparin( ALMWH) and to detect its physico-chemical properties and antineoplastic activity. Meth-ods LMWH was prepared by degradation of UFH with sodium periodate oxidation and sodium borohydride re-duction, then the LMWH was acetylated by acetic an-hydride where N, N′, -dicyclohexylcarbodiimide ( DCC ) and 4-dimethylaminopyridine ( DMAP ) were used as catalysts. X-ray diffraction(XRD)and Differ-ential Scanning Calorimetry ( DSC ) of ALMWH were obtained. The antiproliferative activity and anti-inva-sive activity were determined on MDA-MB-231 and MCE-7 human breast cancer cells. Results XRD a-nalysis showed that the LMWH degraded from UFH and ALMWH synthesized by acetylation of LMWH be-longed to amorphous structure, however, their DSC curves were significantly different. Compared with LM-WH, ALMWH had more powerful capacity for binding water and lowering anticoagulant activity, more signifi-cantly ALMWH exhibited stranger anti-proliferative and anti-invasive activity than LMWH, especially when it was used in low concentrations. Conclusion The syn-thesized ALMWH possesses a low anticoagulant activi-ty, certain anti-proliferative, anti-invasive and anti-metastatic activity. This study provides a basic method for screening of antineoplastic drug with low toxicity.

Preliminary study on preparation of universal blood type through masking RBC’ s surface antigen with Tween / 局解手术学杂志

Objective To explore the shielding effect that Tween has made on the erythrocyte’ s surface antigen( ABO and D antigen mainly) and the stability of the RBC. Methods Various types red blood cells’ surface antigens were incubated with different concentrations of Tween,then the titers of RBC’ s surface antigen before and after incubation were compared. The erythrocyte’ s function alterations and sta-bility through the morphological obersavation,the osmotic fragility,RBC’ s own hemolysis rate,oxygen saturation( SO2 ) ,routine test of blood as well as the supernatant of free hemoglobin determination were confirmed. Results The masking effect of the Tween-20 on D antigen with the weaken titer keeping above“ +” was better and more stable than that on A,B antigen. The impact on B antigen was a little worse,and A was the worst. The advantaged concentration is about 0. 004%. Besides,the influence of Tween-80’s on B and D antigen was not apparent e-nough. Among all of the concentration,0. 74% and 0. 80% did a relatively better job,which also could keep the weaken titer above “ +”. Conclulsion The shielding effect that Tween has made on the erythrocyte’ s surface antigen( ABO and D antigen mainly) is stable,which keeps above “ +”. The morphology and function of the RBC does not change.

Chemical modifications of nucleobases in functional nucleic acids / 国际药学研究杂志

The diversity of functional nucleic acids is being explored from nature and in vitro selections, including ribozyme catalysis, aptamer binding to target molecules with high specific and affinity, and RNA interference and modulation of gene expression. The great potential of chemical and biological activity of four nucleobases and the sugar-phosphate backbone in various specific tertiary structures is beyond our present imagination, and more functions remain to be found. Therefore, developing insight into the structural basis of these functional nucleic acids is invaluable in understanding their mechanisms and exploring the applications. With a special focus on the four nucleobases, we learnt that nucleobases could contribute to the functions by base stacking, electrostatic interactions, complexion with metal ions, hydrogen bonding, and even act as general acid-base in specific functions. Deletion and substitution of each nucleobases demonstrated the conservation of all the natural and unnatural functional nucleic acids. But from the success of chemical modifications at the level of functional groups on 10-23 DNAzyme, there is still room for the optimization of functional nucleic acids, for practical applications as research tools and genetic therapeutics. It is a big challenge for any functional nucleic acids, to conduct the chemical modification in a right way in the complex tertiary structures, including which residue could be used for chemical modification and which functional groups could be introduced for an expected positive effect.

Chemical modifications of nucleobases in functional nucleic acids / 国际药学研究杂志

The diversity of functional nucleic acids is being explored from nature and in vitro selections,including ribozyme catalysis,aptamer binding to target molecules with high specific and affinity,and RNA interference and modulation of gene expression. The great potential of chemical and biological activity of four nucleobases and the sugar-phosphate backbone in various specific tertiary structures is beyond our present imagination,and more functions remain to be found. Therefore,developing insight into the structural basis of these functional nucleic acids is invaluable in understanding their mechanisms and exploring the applications. With a special focus on the four nucleobases,we learnt that nucleobases could contribute to the functions by base stacking,electrostatic interactions,complexion with metal ions,hydrogen bonding,and even act as general acid-base in specific functions. Deletion and substitution of each nucleobases demonstrated the conservation of all the natural and unnatural functional nucleic acids. But from the success of chemical modifications at the level of functional groups on 10-23 DNAzyme,there is still room for the optimization of functional nucleic acids,for practical applications as research tools and genetic therapeutics. It is a big challenge for any functional nucleic acids,to conduct the chemical modification in a right way in the complex tertiary structures, including which residue could be used for chemical modification and which functional groups could be introduced for an expected positive effect.

Mutational analysis for enzyme activity of mouse Gal1,3GalNAc 2,3-sialyltransferase (mST3Gal I).

To determine which amino acid residues are essential for the catalytic activity of mouse Gal1,3GalNAc 2,3-sialyltransferase (mST3Gal I), chemical modification and site-directed mutagenesis were employed against tryptophan and cysteine residues located in the predicted catalytic domain. This enzyme was strongly inhibited by N-bromosuccinimide, a specific blocking reagent for tryptophan residues, and the enzyme activity was completely lost at 3 mM, suggesting the involvement of tryptophan residues in the catalytic activity of mST3Gal I. The N-ethylmaleimide, an irreversible reagent for sulfhydryl group, significantly inhibited the enzyme activity. Seven tryptophan and six cysteine residues conserved in the cloned Gal1,3GalNAc 2,3-sialyltransferases were separately substituted into phenylalanine and serine, respectively. The enzymatic activity assay for tryptophan mutants produced in COS cells showed a complete abolishment of the activity in all of the mutants, except that W70F and W97F retained about 60% and 40% activities of wild type, respectively. In the case of cysteine mutants, no enzyme activity was observed like tryptophan mutants, except for C139S. These results suggest that tryptophan and cysteine residues conserved in ST3Gal I are critical for its activity.

Research progress on derivatives of fucoidan / 国际生物医学工程杂志

Fucoidan is a kind of sulfated polysaccharide with a variety of biological activities.Chemical modification of polysaccharides can improve their bioactivities or make them produce new activities.In order to improve research of fucoidans and gain new polysaccharide drug with high bioactivity,this paper reviews preparative techniques and bioactivities of fucoidan derivatives,including low molecular weight fucoidan,desulfated fucoidan,oversulfated fucoidan,acetylated fucoidan,benzoylated fucoidan,phosphorylated fucoidan,aminated fucoidan and so on.