SELEX was used to create an RNA aptamer targeted to protein tyrosine phosphatase 1B (PTP1B), an enzyme implicated in type 2 diabetes, breast cancer and obesity. We found an aptamer that strongly inhibits PTP1B in vitro with a Ki of less than 600 pM. This slow-binding, high-affinity inhibitor is also highly selective, with no detectable effect on most other tested phosphatases and approximately 300:1 selectivity over the closely related TC-PTP. Through controlled synthesis of truncated variants of the aptamer, we isolated shorter forms that inhibit PTP1B. We also investigated various single-nucleotide modifications to probe their effects on the aptamer's secondary structure and inhibition properties. This family of aptamers represents an exciting option for the development of lead nucleotide-based compounds in combating several human cancers and metabolic diseases.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/cbic.201000208 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Multiple gRNAs-assisted CRISPR/Cas12a-based portable aptasensor enabling glucometer readout for amplification-free and quantitative detection of malathion.
Anal Chim Acta
March 2025
College of New Energy Materials and Chemistry, Leshan Normal University, Leshan, Sichuan, 614000, PR China; Sichuan Province Key Laboratory of Natural Products and Small Molecule Synthesis, Leshan, Sichuan, 614000, PR China. Electronic address:
Background: The threat of toxic malathion residues to human health has always been a serious food safety issue. The CRISPR/Cas system represents an innovative detection technology for pesticide residues, but its application to malathion detection has not been reported yet. In addition, the multiple-guide RNA (gRNA) powered-CRISPR/Cas biosensor has the advantages of being fast, sensitive and does not require pre-amplification.
View Article and Find Full Text PDFMulti-group structure analysis and molecular docking of aptamers and small molecules: A case study of chloramphenicol.
Biochem Biophys Res Commun
January 2025
College of Animal Science and Technology, Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, Guangxi University, Nanning, 530004, Guangxi, China. Electronic address:
Aptamers, a kind of short nucleotide sequences with high specificity and affinity with targets, have attracted extensive attention in recent years. Molecular docking method (MDM) is the most common method to explore the binding mode and recognition mechanism of aptamers and small molecules, which generally use the target to dock with the highest scoring tertiary structural model of the aptamer, and the highest scoring result is used as the predicted model. However, this prediction results may miss out the true interaction pattern due to the fact that aptamers are not completely rigid and the natural aptamers conformations are not in a single state.
View Article and Find Full Text PDFA new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer.
J Nanobiotechnology
January 2025
School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.
Esophageal cancer (EC) is one of the most common highly malignant tumors of the digestive system, with a poor prognosis under current treatment regimens. Nucleolin (NCL) is overexpressed in many tumors, and drugs specifically targeting NCL may offer a promising strategy for treating esophageal cancer. Here, we designed and prepared a novel aptamer-conjugated drug targeting NCL by AS1411 aptamer-human serum albumin (HSA)-the apoprotein of lidamycin (LDP)-active enediyne chromophore (AE), in order to achieve targeted treatment of esophageal cancer.
View Article and Find Full Text PDFElectrochemical capacitance-based aptasensor for HER2 detection.
Biomed Microdevices
January 2025
Department of Physics, Faculty of Philosophy, Science and Letter, University of São Paulo, Ribeirão Preto, SP, 14040-901, Brazil.
The overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) protein is specifically related to tumor cell proliferation in breast cancers. Its presence in biological serum samples indicates presence or progression of cancer, becoming a promise biomarker. However, their detection needs a simple and high accuracy platform.
View Article and Find Full Text PDFAptamer-Conjugated Exosomes Ameliorate Diabetes-Induced Muscle Atrophy by Enhancing SIRT1/FoxO1/3a-Mediated Mitochondrial Function.
J Cachexia Sarcopenia Muscle
February 2025
Department of Endocrinology and Metabolism, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Background: Muscle atrophy is associated with Type 2 diabetes mellitus, which reduces the quality of life and lacks effective treatment strategies. Previously, it was determined that human umbilical cord mesenchymal stromal cell (hucMSC)-derived exosomes (EXOs) ameliorate diabetes-induced muscle atrophy. However, the systemic application of EXOs is less selective for diseased tissues, which reduces their efficacy and safety associated with their nonspecific biological distribution in vivo.
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!