After the recent publication in the Journal of Biophysical Chemistry entitled “Retracted HIV Study Provides New Information about the Status of the in Vitro Inhibition of DNA Replication by Back-bone Methylation”, it is of importance to review the results of Buck’s group on the synthesis and conformation analyses of phosphate-methylated RNAs in order to afford information on the absence of a further investigation with regard to this de facto acceptable approach. In fact these compounds belong to the very first group of RNAs with a modified neutral backbone by phosphatemethylation. In contrast to the corresponding phosphate-methylated DNAs with a frozen B-conformation, the phosphate-methylated RNAs show an A-conformation. The latter is a prerequisite for duplex formation with (complementary) (natural) RNA. A number of experiments support this fundamental statement. After the HIV study was retracted, the overall results concerning the phosphate-methylated RNAs were published without mentioning Buck’s initial proof of concept and his contributions. Generally, the (modified) dimer RNAs and DNAs possess a number of specific biophysical properties. A novel explanation is given for conflicting structural determinations.
{"title":"Modified RNA with a Phosphate-Methylated Backbone. A Serious Omission in Our (Retracted) Study at HIV-1 RNA Loops and Integrated DNA. Specific Properties of the (Modified) RNA and DNA Dimers","authors":"H. Buck","doi":"10.4236/JBPC.2016.71003","DOIUrl":"https://doi.org/10.4236/JBPC.2016.71003","url":null,"abstract":"After the recent publication in the Journal of Biophysical Chemistry entitled “Retracted HIV Study Provides New Information about the Status of the in Vitro Inhibition of DNA Replication by Back-bone Methylation”, it is of importance to review the results of Buck’s group on the synthesis and conformation analyses of phosphate-methylated RNAs in order to afford information on the absence of a further investigation with regard to this de facto acceptable approach. In fact these compounds belong to the very first group of RNAs with a modified neutral backbone by phosphatemethylation. In contrast to the corresponding phosphate-methylated DNAs with a frozen B-conformation, the phosphate-methylated RNAs show an A-conformation. The latter is a prerequisite for duplex formation with (complementary) (natural) RNA. A number of experiments support this fundamental statement. After the HIV study was retracted, the overall results concerning the phosphate-methylated RNAs were published without mentioning Buck’s initial proof of concept and his contributions. Generally, the (modified) dimer RNAs and DNAs possess a number of specific biophysical properties. A novel explanation is given for conflicting structural determinations.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"07 1","pages":"30-41"},"PeriodicalIF":0.0,"publicationDate":"2016-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70904654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Ghazaryan, L. Ghulikyan, V. Chavushyan, N. Ayvazyan
The study has shown free radical processes during modeling of Parkinson Disease (PD) with rotenone. We isolated striatum, brainstem, neocortex, cerebellum, spinal cord, thymus, heart, and liver of rats after rotenone injection in the right striatum. The samples were taken on the 5th, 10th and 15th days after the injection. According to chemiluminescence data, the injection of rotenone initiates the disturbance of intensity of free radical processes in striatum at 5th day in a bilateral mode. After this until the 10th day these changes had restoring character, but after 15 days according to chemiluminescence and thio-barbituric acid test disturbance of lipid peroxide oxidation processes occurred. While superoxide dismutase activity has been changed significantly in all studied tissues, especially in the striatum and neocortex. It should be noted that during rotenone model there are no observed clinical symptoms in rats during 1 to 20 days, and the symptoms of the disease are observed approximately 28 days after the injection. This research could help diagnose PD in the early stage of its onset.
{"title":"Study of Free-Radical Processes during Rotenone Modeling of Parkinson Disease","authors":"N. Ghazaryan, L. Ghulikyan, V. Chavushyan, N. Ayvazyan","doi":"10.4236/JBPC.2016.71001","DOIUrl":"https://doi.org/10.4236/JBPC.2016.71001","url":null,"abstract":"The study has shown free radical processes during modeling of Parkinson Disease (PD) with rotenone. We isolated striatum, brainstem, neocortex, cerebellum, spinal cord, thymus, heart, and liver of rats after rotenone injection in the right striatum. The samples were taken on the 5th, 10th and 15th days after the injection. According to chemiluminescence data, the injection of rotenone initiates the disturbance of intensity of free radical processes in striatum at 5th day in a bilateral mode. After this until the 10th day these changes had restoring character, but after 15 days according to chemiluminescence and thio-barbituric acid test disturbance of lipid peroxide oxidation processes occurred. While superoxide dismutase activity has been changed significantly in all studied tissues, especially in the striatum and neocortex. It should be noted that during rotenone model there are no observed clinical symptoms in rats during 1 to 20 days, and the symptoms of the disease are observed approximately 28 days after the injection. This research could help diagnose PD in the early stage of its onset.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"07 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2016-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70904531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In silico technique was applied to screen potential of 16 compounds of 5,5-dimethylthiohydantoin derivatives as androgen antagonist. The 3D structure of the protein was obtained from PDB database. Docking analysis of the compounds was performed using hex docking. Molecular modeling analysis exhibits relatively low LUMO-HOMO energy gap of the studied molecules, indicating that it would be kinetically stable. None of the compounds violated Lipinski’s parameters, making them potentially promising agents for biological activities. The title compounds exhibited the lowest docking energy of protein-ligand complex. Finally, the results indicate that these compounds are potentially as an androgen antagonist, and expected to be effective in prostate cancer treatment.
{"title":"Molecular Modeling, Docking and ADMET of Dimethylthiohydantoin Derivatives for Prostate Cancer Treatment","authors":"K. Lotfy","doi":"10.4236/JBPC.2015.64010","DOIUrl":"https://doi.org/10.4236/JBPC.2015.64010","url":null,"abstract":"In silico technique was applied to screen potential of 16 compounds of 5,5-dimethylthiohydantoin derivatives as androgen antagonist. The 3D structure of the protein was obtained from PDB database. Docking analysis of the compounds was performed using hex docking. Molecular modeling analysis exhibits relatively low LUMO-HOMO energy gap of the studied molecules, indicating that it would be kinetically stable. None of the compounds violated Lipinski’s parameters, making them potentially promising agents for biological activities. The title compounds exhibited the lowest docking energy of protein-ligand complex. Finally, the results indicate that these compounds are potentially as an androgen antagonist, and expected to be effective in prostate cancer treatment.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"360 1","pages":"91-117"},"PeriodicalIF":0.0,"publicationDate":"2015-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70904488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Sallam, A. Sallam, Elsayed M. Elsayed, L. I. A. Salem, Mona M. Rizk
The aim of the present work is to investigate the effect of the He-Ne laser irradiation on the whole human blood (HB) in order to enhance the conditions of conservation. The HB was irradiated by He-Ne laser; (λ = 632 nm, continuous wave, power 30 mW, 2 mm diameter beam spot), electrical properties and complete blood count CBC were measured at three doses (0.0287, 0.0563 and 0.198 J/cm3) to the relevant best exposure dose during storage periods 9, 24, 30, 35 & 50 days. The irradiation process with the selected dose was performed by the exposure of the laser beam on the blood sample flow through narrow tube of cross section area, 0.0831 cm2. Blood dielectric parameters, (electric conductivity, dielectric constant, dielectric loss and dipole moment) and CBC, (red blood cell, white blood cell, hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and mean cell or corpuscular hemoglobin in concentration) were measured. The obtained results were compared with that of the control and showed that the best irradiation exposure dose suitable for increasing the time of blood storage with minimum changes in properties is 0.198 J/cm3 and storage period of about 50 days. The present study revealed that irradiation by He-Ne laser could be considered a good means to improve the conservation conditions of human blood.
{"title":"Enhancement of Human Blood Storage Period by Irradiation of Low Level He-Ne Laser","authors":"S. Sallam, A. Sallam, Elsayed M. Elsayed, L. I. A. Salem, Mona M. Rizk","doi":"10.4236/JBPC.2015.63008","DOIUrl":"https://doi.org/10.4236/JBPC.2015.63008","url":null,"abstract":"The aim of the present work is to investigate the effect of the He-Ne laser irradiation on the whole human blood (HB) in order to enhance the conditions of conservation. The HB was irradiated by He-Ne laser; (λ = 632 nm, continuous wave, power 30 mW, 2 mm diameter beam spot), electrical properties and complete blood count CBC were measured at three doses (0.0287, 0.0563 and 0.198 J/cm3) to the relevant best exposure dose during storage periods 9, 24, 30, 35 & 50 days. The irradiation process with the selected dose was performed by the exposure of the laser beam on the blood sample flow through narrow tube of cross section area, 0.0831 cm2. Blood dielectric parameters, (electric conductivity, dielectric constant, dielectric loss and dipole moment) and CBC, (red blood cell, white blood cell, hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and mean cell or corpuscular hemoglobin in concentration) were measured. The obtained results were compared with that of the control and showed that the best irradiation exposure dose suitable for increasing the time of blood storage with minimum changes in properties is 0.198 J/cm3 and storage period of about 50 days. The present study revealed that irradiation by He-Ne laser could be considered a good means to improve the conservation conditions of human blood.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"06 1","pages":"77-86"},"PeriodicalIF":0.0,"publicationDate":"2015-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70904405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Intrinsic fluorescence of tryptophan is a powerful tool that is used to investigate structure, dynamics, and folding-unfolding of proteins. Here, we have signified the importance of selective monitoring of “surface” tryptophans from the “buried” tryptophans in a protein via selective excitation of surface tryptophan using light of 305 nm wavelength. We have also enlightened the effect of pH and temperature on the conformation of protein by selective excitation of surface tryptophan of protein using 305 nm light. The result concludes that this novel approach could be used to investigate surface tryptophan of protein selectively at diverse conditions.
{"title":"Investigation of Surface Tryptophan of Protein by Selective Excitation at 305 nm","authors":"V. Tiwari, Monalisa Tiwari","doi":"10.4236/JBPC.2015.63009","DOIUrl":"https://doi.org/10.4236/JBPC.2015.63009","url":null,"abstract":"Intrinsic fluorescence of tryptophan is a powerful tool that is used to investigate structure, dynamics, and folding-unfolding of proteins. Here, we have signified the importance of selective monitoring of “surface” tryptophans from the “buried” tryptophans in a protein via selective excitation of surface tryptophan using light of 305 nm wavelength. We have also enlightened the effect of pH and temperature on the conformation of protein by selective excitation of surface tryptophan of protein using 305 nm light. The result concludes that this novel approach could be used to investigate surface tryptophan of protein selectively at diverse conditions.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"1 1","pages":"87-90"},"PeriodicalIF":0.0,"publicationDate":"2015-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70904437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasushi Yamamoto, T. Yokoyama, D. Yoshida, H. Mori, Karina Sekiguchi, T. Shimoaki, A. Yoshino, K. Taga, Z. Shervani, Masato Yamamoto
The interactions of phospholipid monolayers (dipalmitoyl phosphatidyl choline; DPPC and dimyristoyl phosphatidyl choline; DMPC) with volatile anesthetic isoflurane were investigated using quartz crystal microbalance (QCM) and quartz crystal impedance (QCI) methods. The quartz crystal oscillator was attached horizontally on the surface of DPPC and DMPC monolayer formed on the water surface. Physisorption of isoflurane hydrate at the DPPC monolayer surface was monitored in terms of frequency and resistance change of quartz crystal on addition of anesthetics isoflurane. Both frequency and resistance change showed the elastic nature of DPPC monolayer. Measurement of DMPC monolayer-isoflurane hydrate revealed the expandable nature of DMPC monolayer. Variation of frequency and impedance of DPPC and DMPC monolayer on addition of isoflurane which proved a two-step change has occurred at monolayer surface at isoflurane concentration of ≤8 mM that has been attributed to isoflurane aggregation at monolayer/water interface. Isoflurane hydrates formed in the process have capability to affect the interfacial properties of monolayer such as existence of structured water.
{"title":"Interactions between Phospholipid Monolayers (DPPC and DMPC) and Anesthetic Isoflurane Observed by Quartz Crystal Oscillator","authors":"Yasushi Yamamoto, T. Yokoyama, D. Yoshida, H. Mori, Karina Sekiguchi, T. Shimoaki, A. Yoshino, K. Taga, Z. Shervani, Masato Yamamoto","doi":"10.4236/JBPC.2015.62005","DOIUrl":"https://doi.org/10.4236/JBPC.2015.62005","url":null,"abstract":"The interactions of phospholipid monolayers (dipalmitoyl phosphatidyl choline; DPPC and dimyristoyl phosphatidyl choline; DMPC) with volatile anesthetic isoflurane were investigated using quartz crystal microbalance (QCM) and quartz crystal impedance (QCI) methods. The quartz crystal oscillator was attached horizontally on the surface of DPPC and DMPC monolayer formed on the water surface. Physisorption of isoflurane hydrate at the DPPC monolayer surface was monitored in terms of frequency and resistance change of quartz crystal on addition of anesthetics isoflurane. Both frequency and resistance change showed the elastic nature of DPPC monolayer. Measurement of DMPC monolayer-isoflurane hydrate revealed the expandable nature of DMPC monolayer. Variation of frequency and impedance of DPPC and DMPC monolayer on addition of isoflurane which proved a two-step change has occurred at monolayer surface at isoflurane concentration of ≤8 mM that has been attributed to isoflurane aggregation at monolayer/water interface. Isoflurane hydrates formed in the process have capability to affect the interfacial properties of monolayer such as existence of structured water.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"6 1","pages":"42-53"},"PeriodicalIF":0.0,"publicationDate":"2015-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70903673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ultrafine structure of tendons deposits formed in three patients, males aged 52 and 61 years and a female aged 71 years were evaluated by atomic force microscopy. Three distinctly different structures of deposit surface were identified: (i) compact, smooth and uneven surface composed of closely packed nanoparticles of diameter 30 nm; (ii) surfaces consisting of plate-like crystalline particles about 30 nm thick that formed larger entities divided by deep depressions; (iii) rough surface formed by individual or closely attached elongated needle-like particles with elliptical cross-section of diameter about 30 nm. These surface structures were developed by different formation mechanisms: (i) Aggregation of Posner’s clusters into nanoparticles formed on biological calcific able surfaces and in the bulk of body fluid surrounding the deposits that subsequently settled onto the deposit surface; (ii) Regular crystal growth on surface nuclei generated at low supersaturation of body fluid with respect to the phosphatic phase and/or in a narrow cavity containing a very limited volume of liquid; (iii) Solution mediated re-crystallization of the upper layers of a deposit or unstable crystalline growth governed by volume diffusion of building units to the particle tip. Small rods, 40 nm wide and from 100 to 300 nm long, with no apparent order were detected only on the surface of deposit formed in the female patient. These rods could be debris of collagen fibres that disintegrated into individual building units (macromolecules) with some showing breakdown into smaller fragments.
{"title":"Ultrafine Structure of Calcific Deposits Developed in Calcific Tendinopathy","authors":"M. Zelenková, O. Söhnel, F. Grases","doi":"10.4236/JBPC.2015.62004","DOIUrl":"https://doi.org/10.4236/JBPC.2015.62004","url":null,"abstract":"The ultrafine structure of tendons deposits formed in three patients, males aged 52 and 61 years and a female aged 71 years were evaluated by atomic force microscopy. Three distinctly different structures of deposit surface were identified: (i) compact, smooth and uneven surface composed of closely packed nanoparticles of diameter 30 nm; (ii) surfaces consisting of plate-like crystalline particles about 30 nm thick that formed larger entities divided by deep depressions; (iii) rough surface formed by individual or closely attached elongated needle-like particles with elliptical cross-section of diameter about 30 nm. These surface structures were developed by different formation mechanisms: (i) Aggregation of Posner’s clusters into nanoparticles formed on biological calcific able surfaces and in the bulk of body fluid surrounding the deposits that subsequently settled onto the deposit surface; (ii) Regular crystal growth on surface nuclei generated at low supersaturation of body fluid with respect to the phosphatic phase and/or in a narrow cavity containing a very limited volume of liquid; (iii) Solution mediated re-crystallization of the upper layers of a deposit or unstable crystalline growth governed by volume diffusion of building units to the particle tip. Small rods, 40 nm wide and from 100 to 300 nm long, with no apparent order were detected only on the surface of deposit formed in the female patient. These rods could be debris of collagen fibres that disintegrated into individual building units (macromolecules) with some showing breakdown into smaller fragments.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"253 1","pages":"35-41"},"PeriodicalIF":0.0,"publicationDate":"2015-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70903608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Conditions in rat and turtle small intestine tissue where glucose and glycine transport is inhibited while glucose-induced Na+ transport is preserved are described. The generally accepted model for the Na+-dependent transporter (а single channel for the Na+ and nutrient) does not account for the data obtained from the analysis of the interaction between the transport of glucose, glycine, and Na+ at different temperatures and the effect of inhibitors оn these рroсеssеs. The phenomenon of temperature uncoupling of Na+ and nutrient transport саn best bе described bу а two-pathway model with а gate mechanism. According to this model, the Na+-dependent transporter has at least two pathways: оnе for Na+ and another for nutrients. The model рrovidеs for the passage of Na+ in both directions along а channel opened bу glucose. Experiments are carried out using the addition of glucose and glycine on backgrounds of glycine and glucose, respectively. It has been hypothesized that when all three transporters (for Na+, glucose and glycine) are unite in a single structure, then there should be “competitive relations” between short-circuit current changes on glycine and glucose for sodium ions passing through its transporter.
{"title":"The Physiological Model of Na + -Dependent Transporters for Glucose and Amino Acids in Rat and Turtle","authors":"S. T. Metelsky","doi":"10.4236/JBPC.2015.62007","DOIUrl":"https://doi.org/10.4236/JBPC.2015.62007","url":null,"abstract":"Conditions in rat and turtle small intestine tissue where glucose and glycine transport is inhibited while glucose-induced Na+ transport is preserved are described. The generally accepted model for the Na+-dependent transporter (а single channel for the Na+ and nutrient) does not account for the data obtained from the analysis of the interaction between the transport of glucose, glycine, and Na+ at different temperatures and the effect of inhibitors оn these рroсеssеs. The phenomenon of temperature uncoupling of Na+ and nutrient transport саn best bе described bу а two-pathway model with а gate mechanism. According to this model, the Na+-dependent transporter has at least two pathways: оnе for Na+ and another for nutrients. The model рrovidеs for the passage of Na+ in both directions along а channel opened bу glucose. Experiments are carried out using the addition of glucose and glycine on backgrounds of glycine and glucose, respectively. It has been hypothesized that when all three transporters (for Na+, glucose and glycine) are unite in a single structure, then there should be “competitive relations” between short-circuit current changes on glycine and glucose for sodium ions passing through its transporter.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"06 1","pages":"64-76"},"PeriodicalIF":0.0,"publicationDate":"2015-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70904357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Single nucleotide replacing mutations in genes cause a number of diseases, but sometimes these mutations mimic other genetic mutations such as trinucleotide repeats expansions. A mutation in codon GGG→GCG results in Gly→Ala at the N-terminal of PABPN1 protein that mimics the trinucleotide repeat expansion disease called Oculopharyngeal muscular dystrophy (OPMD). Molecular dynamics simulations in water with peptide models having sequence Ac-A10-GA2GG-NHme (peptide A) and Ac-A10A3GG-NHme (peptide B) reveal an increase in the length of helical segment in peptide B. The α-helical length is found to be stable in peptide B with starting geometry of a right handed helix, while in the case peptide A, the helical length is short. The interactions of water molecules at terminals, side chain-backbone interactions and hydrogen bonds provide stability to resultant conformation. The adopted helix by the poly-Ala stretch may lead to masking some other active parts of the PABPN1 that may trigger the aggregation, decrease in degradation and/or impaired function of protein. Hence, further studies with N-terminal may be helpful to understand unclear disease mechanism.
{"title":"Gly→Ala Point Mutation and Conformation of Poly-Ala Stretch of PABPN1: A Molecular Dynamics Study","authors":"M. Shafique, M. L. Garg, F. S. Nandel","doi":"10.4236/JBPC.2015.62006","DOIUrl":"https://doi.org/10.4236/JBPC.2015.62006","url":null,"abstract":"Single nucleotide replacing mutations in genes cause a number of diseases, but sometimes these mutations mimic other genetic mutations such as trinucleotide repeats expansions. A mutation in codon GGG→GCG results in Gly→Ala at the N-terminal of PABPN1 protein that mimics the trinucleotide repeat expansion disease called Oculopharyngeal muscular dystrophy (OPMD). Molecular dynamics simulations in water with peptide models having sequence Ac-A10-GA2GG-NHme (peptide A) and Ac-A10A3GG-NHme (peptide B) reveal an increase in the length of helical segment in peptide B. The α-helical length is found to be stable in peptide B with starting geometry of a right handed helix, while in the case peptide A, the helical length is short. The interactions of water molecules at terminals, side chain-backbone interactions and hydrogen bonds provide stability to resultant conformation. The adopted helix by the poly-Ala stretch may lead to masking some other active parts of the PABPN1 that may trigger the aggregation, decrease in degradation and/or impaired function of protein. Hence, further studies with N-terminal may be helpful to understand unclear disease mechanism.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"6 1","pages":"54-63"},"PeriodicalIF":0.0,"publicationDate":"2015-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70903356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diego Juscelino Santos Dias, G. Joanitti, R. Azevedo, Luciano P. Silva, C. Lunardi, A. Gomes
The present work aimed to develop and evaluate a colloidal system composed of poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) associated with chlorambucil (CHB) and its effects on cancer cells. The nanoparticles showed %EE (>92%), a mean particle size in the range of 240 to 334 nm and zeta potential of -16.7 to -26.0 mV. In vitro release profile showed a biphasic pattern, with an initial burst for all formulations. The scanning electron microscopy of CHB-nanoparticles showed regular spherical shapes, smooth surface without aggregations. Differential scanning calorimetry thermograms, UV-vis absorption, fluorescence emission and Fourier transform infrared spectroscopy were performed showing the entrapment of the antitumoral in drug delivery system. CHB encapsulated in PLGA nanoparticles decrease the survival rates of the breast cancer cells: 68.9% reduction of cell viability on MCF-7 cell line and 59.7% on NIH3T3. Our results indicated that polymeric nanoparticles produced by classical methods are efficient drug delivery systems for CHB.
{"title":"Chlorambucil Encapsulation into PLGA Nanoparticles and Cytotoxic Effects in Breast Cancer Cell","authors":"Diego Juscelino Santos Dias, G. Joanitti, R. Azevedo, Luciano P. Silva, C. Lunardi, A. Gomes","doi":"10.4236/JBPC.2015.61001","DOIUrl":"https://doi.org/10.4236/JBPC.2015.61001","url":null,"abstract":"The present work aimed to develop and evaluate a colloidal system composed of poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs) associated with chlorambucil (CHB) and its effects on cancer cells. The nanoparticles showed %EE (>92%), a mean particle size in the range of 240 to 334 nm and zeta potential of -16.7 to -26.0 mV. In vitro release profile showed a biphasic pattern, with an initial burst for all formulations. The scanning electron microscopy of CHB-nanoparticles showed regular spherical shapes, smooth surface without aggregations. Differential scanning calorimetry thermograms, UV-vis absorption, fluorescence emission and Fourier transform infrared spectroscopy were performed showing the entrapment of the antitumoral in drug delivery system. CHB encapsulated in PLGA nanoparticles decrease the survival rates of the breast cancer cells: 68.9% reduction of cell viability on MCF-7 cell line and 59.7% on NIH3T3. Our results indicated that polymeric nanoparticles produced by classical methods are efficient drug delivery systems for CHB.","PeriodicalId":62927,"journal":{"name":"生物物理化学(英文)","volume":"25 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2015-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70903266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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