A porphyrin derivative effectively and selectively degraded the target transcription factor, human estrogen receptor-alpha (hER-alpha), upon visible light irradiation, in the absence of additives and under neutral conditions.
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http://dx.doi.org/10.1039/b806961a | DOI Listing |
Sci Adv
January 2025
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Designing binders to target undruggable proteins presents a formidable challenge in drug discovery. In this work, we provide an algorithmic framework to design short, target-binding linear peptides, requiring only the amino acid sequence of the target protein. To do this, we propose a process to generate naturalistic peptide candidates through Gaussian perturbation of the peptidic latent space of the ESM-2 protein language model and subsequently screen these novel sequences for target-selective interaction activity via a contrastive language-image pretraining (CLIP)-based contrastive learning architecture.
View Article and Find Full Text PDFNanoscale
December 2024
School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata - 700032, India.
Lung adenocarcinoma, recognized as one of the most formidable malignancies with a dismal prognosis and low survival rates, poses a significant challenge in its treatment. This article delineates the design and development of a carbon dot-vesicle conjugate (HACD-TMAV) for efficient cytotoxicity towards lung cancer cells by target selective delivery of the glutamine inhibitor 6-diazo-5-oxo-L-norleucine (DON) within CD44-enriched A549 cancer cells. HACD-TMAV is composed of hyaluronic acid-based carbon dots (HACDs) and trimesic acid-based vesicles (TMAV), which are bound electrostatic interactions.
View Article and Find Full Text PDFJ Nucl Med
December 2024
Faculty of Medicine and Health, University of Sydney, Sydney, Australia; and.
Researchers use dynamic PET imaging with target-selective tracer molecules to probe molecular processes. Kinetic models have been developed to describe these processes. The models are typically fitted to the measured PET data with the assumption that the brain is in a steady-state condition for the duration of the scan.
View Article and Find Full Text PDFJ Chem Inf Model
November 2024
OpenEye, Cadence Molecular Sciences, Santa Fe, New Mexico 87508, United States.
J Am Chem Soc
August 2024
Department of Chemistry, National University of Singapore, Singapore 117543, Singapore.
Reversible lysine acetylation is an important post-translational modification (PTM). This process in cells is typically carried out enzymatically by lysine acetyltransferases and deacetylases. The catalytic lysine in the human kinome is highly conserved and ligandable.
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