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1.
PLoS One ; 19(8): e0302339, 2024.
Article in English | MEDLINE | ID: mdl-39208310

ABSTRACT

Although understanding the status of sports participation is essential for preventing injuries in young athletes, the level of specialization and relevant information in Japan is unknown. This study aimed to clarify the status of sports specialization and examine the relationships between specialization and training status in Japanese young soccer players. Four hundred Japanese young male soccer players were included. The players' parents completed a web questionnaire that consisted of three-point questions regarding specialization and training status (year, days of playing soccer, age when starting soccer). The level of specialization and accompanying information were calculated, and data were compared by specialization status. Of the participants, 53.8% demonstrated a high level of specialization. In addition, 74.5% considered soccer more important than other sports, 89.0% trained in soccer for more than 8 months of the year, and 74.0% had quit other sports to focus on soccer or played only soccer. The proportion of participants who played only soccer was significantly higher in the high-specialization group (37.6%) than in the moderate-specialization (22.5%; P < .01) and low-specialization (7.1%; P < .01) groups. By specialization status at grades 4 to 6 (9-12 years), 40.3% of participants demonstrated a high level of specialization. Young Japanese soccer players tend toward early specialization. Factors contributing to the high specialization level are being active throughout the year and rarely playing other sports. Training volume should be controlled, and an environment allowing young soccer players to participate in other sports simultaneously is needed, with early specialization being avoided.


Subject(s)
Athletes , Soccer , Humans , Male , Japan , Child , Adolescent , Athletes/statistics & numerical data , Surveys and Questionnaires , Specialization , East Asian People
2.
Chem Commun (Camb) ; 59(57): 8862-8865, 2023 Jul 13.
Article in English | MEDLINE | ID: mdl-37377065

ABSTRACT

Thrombin-binding aptamer (TBA), which forms a G-quadruplex (G4) structure with anti-parallel topology, interacts with thrombin to inhibit its enzymatic activity. Here we show that the G4-topology-altering ligand L2H2-2M2EA-6LCO (6LCO) changes the anti-parallel topology of TBA G4 to the parallel topology, thereby abrogating the thrombin-inhibitory activity of TBA. This finding suggests that G4 ligands that alter topology may be promising drug candidates for diseases involving G4-binding proteins.


Subject(s)
Aptamers, Nucleotide , G-Quadruplexes , Thrombin/chemistry , Ligands , Aptamers, Nucleotide/chemistry
3.
Chem Commun (Camb) ; 59(44): 6678-6681, 2023 May 30.
Article in English | MEDLINE | ID: mdl-37165738

ABSTRACT

Click reactions are used for chemoselective functionalization in many research fields. Despite the utility of small, bioinert azide groups as a counterpart, applications of strain-promoted alkyne-azide cycloaddition (SPAAC) reactions for this purpose are still limited by slow reaction kinetics. Here, we report ion-pair-guided reaction rate enhancement by the use of water-soluble cyclooctadiynes (WS-CODYs) composed of bifunctional strained alkynes and polar side chains. Arrhenius plot analysis revealed that the rate enhancement by WS-CODYs is due to a kinetic salt effect between the polar substituents and the target azide. We demonstrate the utility of these compounds for rapid protein labelling and isoelectric point-dependent labelling.

4.
J Cell Sci ; 135(24)2022 12 15.
Article in English | MEDLINE | ID: mdl-36444566

ABSTRACT

Polarized transport is essential for constructing multiple plasma membrane domains in the cell. Drosophila photoreceptors are an excellent model system to study the mechanisms of polarized transport. Rab11 is the key factor regulating the post-Golgi transport of rhodopsin 1 (Rh1; also known as NinaE), a photoreceptive protein, to the rhabdomere, a photoreceptive plasma membrane. Here, we found that neuronal Synaptobrevin (nSyb) colocalizes with Rab11 on the trans-side of Golgi stacks and post-Golgi vesicles at the rhabdomere base, and nSyb deficiency impairs rhabdomeric transport and induces accumulation of Rh1 and vesicles in the cytoplasm; this is similar to the effects of Rab11 loss. These results indicate that nSyb acts as a post-Golgi SNARE toward rhabdomeres. Surprisingly, in Rab11-, Rip11- and nSyb-deficient photoreceptors, illumination enhances cytoplasmic accumulation of Rh1, which colocalizes with Rab11, Rabenosyn5, nSyb and Arrestin 1 (Arr1). Arr1 loss, but not Rab5 dominant negative (Rab5DN) protein expression, inhibits the light-enhanced cytoplasmic Rh1 accumulation. Rab5DN inhibits the generation of Rh1-containing multivesicular bodies rather than Rh1 internalization. Overall, these results indicate that exocytic Rh1 mingles with endocytosed Rh1 and is then transported together to rhabdomeres.


Subject(s)
Drosophila Proteins , Drosophila , Animals , Drosophila/metabolism , Rhodopsin/metabolism , Photoreceptor Cells, Invertebrate/metabolism , Drosophila Proteins/metabolism , R-SNARE Proteins/metabolism , rab5 GTP-Binding Proteins/metabolism , Drosophila melanogaster/metabolism
5.
Anal Biochem ; 649: 114693, 2022 07 15.
Article in English | MEDLINE | ID: mdl-35500657

ABSTRACT

Binding between a ligand and a receptor is a fundamental step in many natural or synthetic processes. In biosensing, a tight binding with a small dissociation constant (Kd) between the probe and analyte can lead to superior specificity and sensitivity. Owing to their capability of evaluating competitors, displacement assays have been used to estimate Kd at the ensemble average level. At the more sensitive single-molecule level, displacement assays are yet to be established. Here, we developed a single-molecule displacement assay (smDA) in an optical tweezers instrument and used this innovation to evaluate the binding of the L2H2-6OTD ligands to human telomeric DNA G-quadruplexes. After measuring Kd of linear and dendrimer L2H2-6OTD ligands, we found that dendrimer ligands have enhanced binding affinity to the G-quadruplexes due to their polyvalent geometry. This increased binding affinity enhanced inhibition of telomerase elongation on a telomere template in a Telomerase Repeated Amplification Protocol (TRAP). Our experiments demonstrate that the smDA approach can efficiently evaluate binding processes in chemical and biological processes.


Subject(s)
Dendrimers , G-Quadruplexes , Telomerase , Humans , Ligands , Telomerase/metabolism , Telomere/metabolism
6.
J Strength Cond Res ; 36(6): 1715-1719, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-32639378

ABSTRACT

ABSTRACT: Koyama, T, Rikukawa, A, Nagano, Y, Sasaki, S, Ichikawa, H, and Hirose, N. Acceleration profile of high-intensity movements in basketball games. J Strength Cond Res 36(6): 1715-1719, 2022-This study aimed to elucidate movements that require greater acceleration during basketball games, their occurrence frequency, and compare acceleration components. Eighteen male collegiate basketball players (age: 19.5 ± 0.8 years) were enrolled. Triaxial accelerometer was used to measure acceleration and a synchronized video was recorded. Moments that generated resultant accelerations >4, 6, and 8 G, and their coincided movements were identified. Ratios and frequencies of the extracted movements were calculated and Jonckheere-Terpstra trend test was used to examine which movement rate increased when acceleration threshold increased. In addition, the top 7 movements that generated a resultant acceleration >6 G among the combination of basketball-specific movements were extracted. Their resultant, mediolateral, vertical, and anteroposterior accelerations were identified and compared using one-way analysis of variance. Cohen's d was used to calculate effect sizes. All p < 0.05 were considered statistically significant. The extracted frequencies were 33.6, 9.1, and 2.3 cases per minute for >4 G, >6 G, and >8 G, respectively. As the threshold increased, the rate of deceleration, landing, and physical contact increased. The mediolateral acceleration of physical contact was significantly greater than other movements, whereas the vertical acceleration of landing and deceleration was significantly greater than other movements. Thus, acceleration component analysis was performed to classify movement types. Greater acceleration appeared frequently in movement during defense. It is suggested that many defense movements involve a reaction to the ball and opponent. There are many passive movements during defense and speed changes rapidly. If many passive movements occur when defending, larger physical load is applied, and may lead to fatigue.


Subject(s)
Basketball , Acceleration , Adolescent , Adult , Fatigue , Humans , Male , Movement , Universities , Young Adult
7.
Sports Biomech ; 21(10): 1160-1175, 2022 Nov.
Article in English | MEDLINE | ID: mdl-32326846

ABSTRACT

The magnitude of trunk acceleration reflects the ground reaction force. This study compared the frequency of high trunk accelerations during single-leg landing after an overhead stroke between junior and adolescent badminton players, and examined the difference in each directive magnitude according to age and landing leg. Thirty-eight female badminton players (17 junior and 21 adolescent athletes) played two singles games while wearing a tri-axial accelerometer on their upper back. The frequency and 95% confidence interval (CI) of single-leg landings that generated >4-G resultant acceleration, and each directive magnitude were calculated. A two-factorial analysis of variance (factor 1: group, factor 2: landing leg) was performed to determine the effects of age and different landing patterns. Frequency of single-leg landings following an overhead stroke in the adolescent athletes (mean, 1.71 cases/min; 95% CI, 1.59-1.83 cases/min) was higher than that in the junior athletes (mean, 1.13 cases/min; 95% CI, 1.01-1.25 cases/min). The adolescent athletes exhibited greater mediolateral acceleration in the movement towards racket-hand leg and anteroposterior acceleration in the movement towards the opposite leg than the junior athletes. This cross-sectional study suggests that the frequency and movement pattern associated with high-load landing in badminton games differ between junior and adolescent athletes.


Subject(s)
Racquet Sports , Stroke , Acceleration , Adolescent , Athletes , Biomechanical Phenomena , Cross-Sectional Studies , Female , Humans , Leg
8.
Int J Sports Physiol Perform ; 17(1): 16-21, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34186509

ABSTRACT

PURPOSE: To evaluate the effect of the number of high-acceleration movements on muscle damage and the rating of perceived exertion (RPE) in basketball games. METHODS: Twenty-one male collegiate basketball players (mean age, 20.0 [1.0] y) were included. A triaxial accelerometer was used to measure acceleration in basketball-simulated scrimmages. To detect higher physical load during the actual game, the resultant acceleration was calculated, and 3 thresholds were set: >4G, >6G, and >8G resultant accelerations. The number of the extracted movements was calculated at each acceleration threshold. Plasma creatine kinase (CK) levels (marker of muscle damage) were estimated before and 24 hours after the match, and the session-RPE load was calculated within 30 minutes after the match. Pearson product-moment correlations with 95% confidence intervals were used to determine the relationships between the number of high-acceleration movements and plasma CK and session-RPE load. RESULTS: Significant correlations were observed between the number of high-acceleration movements >8G and CK level (r = .74; 95% confidence interval, 0.44-0.89; P < .0001). Furthermore, the correlation coefficient between acceleration and CK increased with increased acceleration threshold (>4G: r = .65; >6G: r = .69). Contrastingly, the correlation coefficient between acceleration and the session-RPE load decreased with increased acceleration threshold (>4G: r = .72; >6G: r = .52; >8G: r = .43). CONCLUSIONS: The session-RPE reflects the total amount of movement, while the high-acceleration movement reflects the momentary large impact load or intensity, and they evaluated different factors. Basketball coaching and conditioning professionals recommended combining acceleration and session-RPE when monitoring the load of athletes.


Subject(s)
Basketball , Physical Conditioning, Human , Acceleration , Adult , Humans , Male , Muscles , Physical Exertion , Young Adult
9.
J Sports Sci ; 40(4): 431-441, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34727847

ABSTRACT

Hamstring strain often occurs when an opponent unanticipatedly perturbs an athlete's movements. We examined the neuromuscular responses of hamstring and trunk muscles during unanticipated trunk perturbations in athletes with and without a history of hamstring strain injury. Male college athletes (11 with a history of a unilateral hamstring injury and 10 without prior injury) knelt while wearing a chest harness attached to a cable that was pulled backward. They were instructed to resist the force isometrically and maintain their position when the perturbations were applied. The pressure was released with or without a cue (CUE or NoCUE). We measured trunk acceleration, three-dimensional kinematic data, and surface electromyography (EMG) signals of the erector spinae, internal oblique, gluteus maximus, biceps femoris long head, and semitendinosus muscles. Maximum trunk acceleration and displacement were greater with NoCUE in both groups (p < 0.05). EMG amplitude did not differ after perturbation of any investigated muscle. The injured group demonstrated a delayed onset of the gluteus maximus and erector spinae muscles in NoCUE versus CUE stimuli (p < 0.05). Athletes with a history of hamstring strain injury exhibited a reduced neuromuscular coordination of the lumbopelvic muscles in response to unanticipated trunk movement.


Subject(s)
Hamstring Muscles , Biomechanical Phenomena , Electromyography , Humans , Male , Muscle, Skeletal/physiology , Paraspinal Muscles , Torso
10.
Sports Biomech ; : 1-15, 2021 Sep 07.
Article in English | MEDLINE | ID: mdl-34490829

ABSTRACT

Repetitive high-impact movements cause growth-related injuries in children. This study aimed to identify which movements during junior football games require >6 G and >8 G acceleration and the frequency at which they occur. Additionally, we compared the components of acceleration among movements with >8 G resultant acceleration. Eleven young male footballers (10.7 ± 0.4 years) played 8-a-side games while wearing a tri-axial accelerometer on their upper back. The number and frequency of the movements that generated >6 G and >8 G were calculated, and each directive acceleration of the top five items was compared using two-way ANOVA to examine the effect of movements. The frequency of movements that generated >6 G and >8 G acceleration during junior football games was 8.70 case/min and 2.62 case/min, respectively. The top five >8 G movements were braking and pre-braking in shuffle, slowdown, stop, and run/jog items. The vertical acceleration was significantly greater during braking in shuffle than during slowdown, stop, and run/jog and also greater during stop and pre-braking in shuffle than during run/jog movement. This pilot study suggests that decelerated movements mainly provoked high-impact situations and may be key actions for preventing overuse injury in young footballers.

11.
Chem Commun (Camb) ; 57(59): 7236-7239, 2021 Jul 28.
Article in English | MEDLINE | ID: mdl-34263271

ABSTRACT

The extent of thermodynamic stabilization of telomeric G-quadruplex (G4) by isomers of G4 ligand L2H2-6OTD, a telomestatin analog, is inversely correlated with susceptibility to S1 nuclease. L2H2-6OTD facilitated the S1 nuclease activities through the base flipping in G4, unlike the conventional role of G4 ligands which inhibit the protein binding to DNA/RNA upon ligand interactions.


Subject(s)
G-Quadruplexes , Single-Strand Specific DNA and RNA Endonucleases/metabolism , Isomerism , Ligands , Nucleic Acid Conformation , Oxazoles/chemistry , Telomere/chemistry , Thermodynamics
12.
Sports Med Int Open ; 5(1): E22-E27, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33553596

ABSTRACT

This study aimed to identify the high-impact details of play and movements with higher acceleration and their frequency during a female basketball match. Trunk acceleration was measured during a simulated basketball game with eight female players. The extracted instance was categorized, which generated at > 6 and 8 G resultant accelerations using a video recording and an accelerometer attached to the players' trunk, as details of play and movements. The frequency and ratio of the details of play and movements regarding all detected movements were calculated. A total of 1062 and 223 play actions were detected for the resultant acceleration thresholds of > 6 and 8 G, respectively. For these acceleration thresholds, in terms of details of play, positioning on the half-court was the most frequently observed (29.6 and 23.8%, respectively). In terms of movements, deceleration was the most frequently detected movement (21.5 and 23.3%, respectively), followed by landing (7.6 and 15.7%, respectively). Deceleration during positioning on the half-court and defense as well as landing mostly after a shot were detected as high-impact frequent basketball-specific movements. The results also showed that characteristics of movements or playing style and playing position may have an effect on acceleration patterns during a basketball game.

13.
Org Biomol Chem ; 19(13): 2891-2894, 2021 04 07.
Article in English | MEDLINE | ID: mdl-33570069

ABSTRACT

The selective alkylation of nucleic acids is important for a medicinal approach and biological study. We now report a novel selective alkylation of the parallel G-quadruplex structure using the conjugate of the macrocyclic hexaoxazole L2G2-6OTD-1M1PA and vinyl-quinazolinone-S(O)Me (6OTD-VQ-S(O)Me).


Subject(s)
DNA/chemical synthesis , Macrocyclic Compounds/chemistry , Oxazoles/chemistry , Quinazolinones/chemistry , Vinyl Compounds/chemistry , Alkylation , DNA/chemistry , G-Quadruplexes , Molecular Structure
14.
Bioorg Med Chem ; 28(18): 115668, 2020 09 15.
Article in English | MEDLINE | ID: mdl-32828430

ABSTRACT

Antisense oligonucleotides (AS-ODNs) specifically hybridize with target mRNAs, resulting in interference with the splicing mechanism or the regulation of protein translation. In our previous reports, we demonstrated that ß-glucan schizophyllan (SPG) can form a complex with AS-ODNs attached with oligo deoxyadenosine dA40 (AS-ODN-dA40/SPG), and that this complex can be recognized by ß-glucan receptor Dectin-1 on antigen presenting cells and lung cancer cells. In many types of cancer cell, activating K-ras mutations related to malignancy are frequently observed. In this study, we first designed 78 AS-ODNs for K-ras to optimize the sequence for highly efficient gene suppression. The selected AS-ODN (K-AS07) having dA40 made a complex with SPG. The resultant complex (K-AS07-dA40/SPG) showed an effect of silencing the ras gene in the cells (PC9: human adenocarcinoma differentiated from lung tissue) expressing Dectin-1, leading to the suppression of cell growth. Furthermore, the cytotoxic effect was enhanced when used in combination with the anticancer drug gemcitabine. Gemcitabine, a derivative of cytidine, was shown to interact with dA40 in a sequence-dependent manner. This interaction did not appear to be so strong, with the gemcitabine being released from the complex after internalization into the cells. SPG and the dA40 part of K-AS07-dA40 play roles in carriers for K-AS07 and gemcitabine, respectively, resulting in a strong cytotoxic effect. This combination effect is a novel feature of the AS-ODN-dA40/SPG complexes. These results could facilitate the clinical application of these complexes for cancer treatment.


Subject(s)
Antineoplastic Agents/chemistry , Cell Cycle/drug effects , Deoxycytidine/analogs & derivatives , Lung Neoplasms/drug therapy , Oligonucleotides, Antisense/chemistry , Sizofiran/chemistry , Amino Acid Sequence , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cells, Cultured , Deoxycytidine/chemistry , Deoxycytidine/pharmacology , Drug Delivery Systems , Drug Liberation , Drug Therapy, Combination , Humans , Lectins, C-Type/genetics , Lectins, C-Type/metabolism , Oligonucleotides, Antisense/pharmacology , Sizofiran/pharmacology , Gemcitabine
15.
Sports Biomech ; 19(3): 342-352, 2020 Jun.
Article in English | MEDLINE | ID: mdl-29912632

ABSTRACT

This study aimed to elucidate the movements requiring greater trunk accelerations and its frequencies during badminton games, and compare the acceleration components among such movements. Trunk acceleration was measured using a triaxial accelerometer during badminton games. The moments that generated >4 G resultant acceleration were extracted, and movements consistent with the extracted moments were identified. We calculated the extracted movement ratio and frequency and compared the resultant, mediolateral, vertical and anteroposterior accelerations between the top five extracted movements. There were 1,342 movements that generated >4 G [mean, 7.72 (95% confidence interval, 7.31-8.14) cases/min]. The top five movements were lunging during underhand strokes with the dominant hand side leg, landing after overhand strokes on the dominant and non-dominant hand side leg, and cutting from a split step using the dominant and non-dominant hand side leg. Landing on the dominant hand side leg had a greater resultant acceleration than the other movements and had the greatest impact during the badminton game. Lunging during underhand strokes on the dominant hand side leg had greater mediolateral acceleration than the other movements. These results reflected the properties of badminton.


Subject(s)
Movement/physiology , Racquet Sports/physiology , Torso/physiology , Acceleration , Accelerometry/instrumentation , Adolescent , Biomechanical Phenomena , Female , Humans , Time and Motion Studies , Wearable Electronic Devices
16.
RSC Adv ; 10(71): 43319-43323, 2020 Nov 27.
Article in English | MEDLINE | ID: mdl-35519695

ABSTRACT

G-quadruplex structures (G4s) in guanine-rich regions of DNA play critical roles in various biological phenomena, including replication, translation, and gene expression. There are three types of G4 topology, i.e., parallel, anti-parallel, and hybrid, and ligands that selectively interact with or stabilize a specific topology have been extensively explored to enable studies of topology-related functions. Here, we describe the synthesis of a new series of G4 ligands based on 6LCOs (6-linear consecutive oxazoles), i.e., L2H2-2M2EA-6LCO (2), L2A2-2M2EAc-6LCO (3), and L2G2-2M2EG-6LCO (4), which bear four aminoalkyl, acetamidealkyl, and guanidinylalkyl side chains, respectively. Among them, ligand 2 stabilized telomeric G4 and induced anti-parallel topology independently of the presence of cations. The anti-parallel topology induced by 2 was identified as chair-type by means of 19F NMR spectroscopy and fluorescence experiments with 2-aminopurine-labeled DNA.

17.
ACS Nano ; 13(8): 9218-9226, 2019 Aug 27.
Article in English | MEDLINE | ID: mdl-31394038

ABSTRACT

The ideal quantum confinement structure of monolayer semiconductors offers prominent optical modulation capabilities that are mediated by enhanced many-body interactions. Herein, we establish an electrolyte-gating method for tuning the luminescence properties that are in transition metal dichalcogenide (TMDC) monolayers. We fabricate electric double-layer capacitors on TMDC/graphite heterostructures to investigate electric-field- and carrier-density-dependent photoluminescence. The exciton peak energy initially shows a slight quadratic red shift of ∼1 meV without carrier accumulations, which is caused by the quantum-confined Stark effect. In contrast, the exciton resonance exhibits a larger red shift up to 10 meV with the accumulated carrier density above 1013 cm-2. These results indicate that the optical transitions can be largely modulated by the carrier density control in S- and Se-based TMDCs, as triggered by the doping-induced band gap renormalization effect. To further inspire this modulation capability, we also apply our method to electrolyte-based TMDC light-emitting devices. Biasing solely in electrolyte-induced p-i-n junctions yields pronounced red shifts up to 40 meV for exciton and trion electroluminescence. Consequently, our approach reveals that the doping effects in the high-carrier-density regimes are potentially significant for efficient optical modulation in monolayer semiconductors.

18.
Nat Commun ; 10(1): 3709, 2019 Aug 16.
Article in English | MEDLINE | ID: mdl-31420551

ABSTRACT

High-harmonic generation in solids is a unique tool to investigate the electron dynamics in strong light fields. The systematic study in monolayer materials is required to deepen the insight into the fundamental mechanism of high-harmonic generation. Here we demonstrated nonperturbative high harmonics up to 18th order in monolayer transition metal dichalcogenides. We found the enhancement in the even-order high harmonics which is attributed to the resonance to the band nesting energy. The symmetry analysis shows that the valley polarization and anisotropic band structure lead to polarization of the high-harmonic radiation. The calculation based on the three-step model in solids revealed that the electron-hole polarization driven to the band nesting region should contribute to the high harmonic radiation, where the electrons and holes generated at neighboring lattice sites are taken into account. Our findings open the way for attosecond science with monolayer materials having widely tunable electronic structures.

19.
Molecules ; 24(2)2019 Jan 11.
Article in English | MEDLINE | ID: mdl-30642002

ABSTRACT

G-quadruplexes (G4s), which are structures formed in guanine-rich regions of DNA, are involved in a variety of significant biological functions, and therefore "sequence-dependent" selective G4-stabilizing agents are required as tools to investigate and modulate these functions. Here, we describe the synthesis of a new series of macrocyclic hexaoxazole-type G4 ligand (6OTD) bearing three side chains. One of these ligands, 5b, stabilizes telomeric G4 preferentially over the G4-forming DNA sequences of c-kit and K-ras, due to the interaction of its piperazinylalkyl side chain with the groove of telomeric G4.


Subject(s)
G-Quadruplexes/drug effects , Oxazoles/chemistry , Oxazoles/pharmacology , Telomere/chemistry , Telomere/drug effects , Chemistry Techniques, Synthetic , Circular Dichroism , Humans , Ligands , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Quantitative Structure-Activity Relationship
20.
Angew Chem Int Ed Engl ; 58(3): 877-881, 2019 01 14.
Article in English | MEDLINE | ID: mdl-30476359

ABSTRACT

Mechanical anisotropy is an essential property for biomolecules to assume structural and functional roles in mechanobiology. However, there is insufficient information on the mechanical anisotropy of ligand-biomolecule complexes. Herein, we investigated the mechanical property of individual human telomeric G-quadruplexes bound to telomestatin, using optical tweezers. Stacking of the ligand to the G-tetrad planes changes the conformation of the G-quadruplex, which resembles a balloon squeezed in certain directions. Such a squeezed balloon effect strengthens the G-tetrad planes, but dislocates and weakens the loops in the G-quadruplex upon ligand binding. These dynamic interactions indicate that the binding between the ligand and G-quadruplex follows the induced-fit model. We anticipate that the altered mechanical anisotropy of the ligand-G-quadruplex complex can add additional level of regulations on the motor enzymes that process DNA or RNA molecules.


Subject(s)
G-Quadruplexes/drug effects , Oxazoles/chemistry , Oxazoles/pharmacology , Anisotropy , Biomechanical Phenomena , Humans , Models, Molecular
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