Aberrant RNA-binding proteins form the core of the neurodegeneration cascade in spectrums of disease, such as amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Six ALS-related molecules, TDP-43, FUS, TAF15, EWSR1, heterogeneous nuclear (hn)RNPA1 and hnRNPA2 are RNA-binding pro...
Christos A.Nicolaou,NathanBrown, inDrug Discovery Today: Technologies, 2013 De novodesign De novodesign is an effort to design chemical compounds using knowledge on the pharmaceutical target site or its available ligands [2]. To design products that are truly of interest to thedrug discoveryresearc...
We describe a de novo computational approach for designing proteins that recapitulate the binding sites of natural cytokines, but are otherwise unrelated in topology or amino acid sequence. We use this strategy to design mimics of the central immune cytokine interleukin-2 (IL-2) that bind to the...
ADVANCES IN DE NOVO PROTEIN DESIGN FOR MONOMERIC, MULTIMERIC, AND CONFORMATIONAL SWITCH PROTEINSThe aim ofde novoprotein design is to find the amino acid sequences that will fold into a desired 3-dimensional structure with improvements in specific properties, such as binding affinity, agonist or ...
Many peptide hormones form an α-helix on binding their receptors, and sensitive methods for their detection could contribute to better clinical management of disease. De novo protein design can now generate binders with high affinity and specificity to structured proteins. However, the design of int...
We present our approach based on de novo structure-based drug design. Using known structural information from complexes engaging opposing members of the BCL-2 family of proteins, we designed peptidomimetic compounds using a benzoylurea scaffold to reproduce key interactions between these proteins. A ...
Thus these proteins constitute complex folds, making de novo computational structure prediction challenging (Bonneau et al., 2002a). In order to mimic cryo-EM density maps, simulated density maps at 6.9 and 9.0 Å resolution were generated for each of the ten proteins. The positions and ...
Presently, hydrogel nanoparticles find ubiquitous applications across various domains, including but not limited to the following [135]: augmenting the stability and bioavailability of drugs to enhance the efficiency and effectiveness of drug delivery. They play a pivotal role in cell culture and tissue...
Enabling future drug discovery by de novo design. Wiley Interdisciplinary Reviews: Computational Molecular Science, 1(5):742-759, 2011.Hartenfeller, M. & Schneider, G. Enabling future drug discovery by de novo design. Wiley Interdisciplinary Reviews: Computational Molecular Science 1, 742-759 (...
BMS-986165结构式,de novo结构氘代药物 (自我研发,未借鉴其他企业原始分子) SWOT analysis of the deuteration approach 中国国家药品监督管理局于2022年7月15日受理其上市申请。本品在中国获批主要依据POETYK PSO-3临床试验(NCT04167462):一项多中心、随机、双盲、安慰剂对照的III期临床研究,旨在评估颂狄多(氘可来昔...