Aim: To study the role of mRNA secondary structure stability in antisense drug design and obtain better antisense candidates against neu/HER-2/erbB-2 mRNA than previous report.
Methods: Program RNAstructure was utilized to simulate the secondary structures of HER-2 mRNA. Then 21 antisense phosphorothioate oligodeoxynucleotides (S-ODN) targeting different parts of secondary structural motif were designed. HA4 was set as positive control. Mean 50 % inhibitory effects (IC(50)) of S-ODN on proliferations of SK-BR-3 breast cancer cells were evaluated. The expression of target mRNA was detected by RT-PCR. The multiple regression and quantitative structure-activity relationship (QSAR) analysis was preformed by SPSS software.
Results: One optimal and two suboptimal secondary structures of target mRNA were obtained. Nine out of 11 S-ODN against completely conservative local motif (LM) (conservative among all simulant secondary structures) got lower or similar IC(50) values compared with HA4. On the other hand, 2 out of 3 S-ODN against relatively conservative LM (conservative between any two simulant secondary structures) got lower or similar IC(50) values compared with HA4. Only 2 out of 5 S-ODN targeting variable LM (variable among different predicted secondary structures) had acceptable activities. Average IC(50) of S-ODN against completely conservative LM was significantly lower than that of S-ODN against diverse LM. QSAR analysis suggested that stability, base number of bulge loops, and target free energies Delta GoT were statistically significant. In the multiple regression, R was 0.967, P=0.005.
Conclusion: Antisense drug design against conservative LM was helpful for improving the positive rate. Several S-ODN candidates better than positive control were screened.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
New acorane-sesequiterpenes and anti-retinoblastoma constituents from the marine algicolous fungus Trichoderma harzianum NTU2180 guided by molecular networking strategy.
Bot Stud
January 2025
Institute of Fisheries Science, College of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Da'an Dist, Taipei, 106319, Taiwan (R.O.C.).
Background: Trichoderma species, known as biocontrol agents against plant diseases, contain diverse compounds, especially terpenoids, with various bioactivities. To facilitate the exploration of bioactive secondary metabolites of Trichoderma harzianum NTU2180, the OSMAC approach MS/MS molecular networking was applied in the current study.
Results: The feature-based molecular networking (FBMN) analysis showed that T.
Privacy-ensuring Open-weights Large Language Models Are Competitive with Closed-weights GPT-4o in Extracting Chest Radiography Findings from Free-Text Reports.
Radiology
January 2025
From the Department of Diagnostic and Interventional Radiology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
Background Large-scale secondary use of clinical databases requires automated tools for retrospective extraction of structured content from free-text radiology reports. Purpose To share data and insights on the application of privacy-preserving open-weights large language models (LLMs) for reporting content extraction with comparison to standard rule-based systems and the closed-weights LLMs from OpenAI. Materials and Methods In this retrospective exploratory study conducted between May 2024 and September 2024, zero-shot prompting of 17 open-weights LLMs was preformed.
View Article and Find Full Text PDFThe endothelium at the interface between tissues and in the bloodstream.
Clin Microbiol Rev
January 2025
Laboratory of Pathology of Implant Infections, Laboratory of Immunorheumatology and Tissue Regeneration, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
SUMMARY is a major human pathogen. It can cause many types of infections, in particular bacteremia, which frequently leads to infective endocarditis, osteomyelitis, sepsis, and other debilitating diseases. The development of secondary infections is based on the bacterium's ability to associate with endothelial cells lining blood vessels.
View Article and Find Full Text PDFPerson-centered support for patients with a pituitary tumor following surgery.
Endocr Connect
January 2025
G Johannsson, Department of internal medicine and clinical nutrition, University of Gothenburg Institute of Medicine, Goteborg, Sweden.
Objective: To evaluate whether a person-centered care practice following surgery for pituitary tumors increased psychological well-being. Secondary aims were to study whether person-centered care would lead to better health status, less fatigue, and better self-efficacy.
Design And Methods: The study is a prospective, single center study using a quasi-experimental design to evaluate the effect of a 12-month person-centered practice by means of a name-given nurse care manager, an interdisciplinary team, and peer-support against usual care.
Green Synthesis of Silver-Doped ZnO Nanoparticles From Adiantum venustum D. Don (Pteridaceae): Antimicrobial and Antioxidant Evaluation.
J Basic Microbiol
January 2025
Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.
One of the main difficulties in nanotechnology is the development of an environmentally friendly, successful method of producing nanoparticles from biological sources. Silver-doped zinc oxide nanoparticles (Ag-ZnO NPs), with antibacterial and antioxidant properties, were produced using Adiantum venustum extract as a green technique. Fresh A.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!