Aiping Dong
YOU?
Author Swipe
View article: Structural basis of TMPRSS11D specificity and autocleavage activation
Structural basis of TMPRSS11D specificity and autocleavage activation Open
Transmembrane Protease, Serine-2 (TMPRSS2) and TMPRSS11D are human proteases that enable SARS-CoV-2 and Influenza A/B virus infections, but their biochemical mechanisms for facilitating viral cell entry remain unclear. We show these protea…
View article: High-throughput protein target mapping enables accelerated bioactivity discovery for ToxCast and PFAS compounds
High-throughput protein target mapping enables accelerated bioactivity discovery for ToxCast and PFAS compounds Open
Chemical pollution is a global threat to human health, yet the toxicity mechanism of most contaminants remains unknown. Here, we applied an ultrahigh-throughput affinity-selection mass spectrometry (AS-MS) platform to systematically identi…
View article: Enantioselective Protein Affinity Selection Mass Spectrometry (E-ASMS)
Enantioselective Protein Affinity Selection Mass Spectrometry (E-ASMS) Open
We report an enantioselective protein affinity selection mass spectrometry screening approach (E-ASMS) that enables the detection of weak binders, informs on selectivity, and generates orthogonal confirmation of binding. After method devel…
View article: A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins
A Target Class Ligandability Evaluation of WD40 Repeat-Containing Proteins Open
Target class-focused drug discovery has a strong track record in pharmaceutical research, yet public domain data indicate that many members of protein families remain unliganded. Here we present a systematic approach to scale up the discov…
View article: Enabling Open Machine Learning of DNA Encoded Library Selections to Accelerate the Discovery of Small Molecule Protein Binders
Enabling Open Machine Learning of DNA Encoded Library Selections to Accelerate the Discovery of Small Molecule Protein Binders Open
Recent advances in DNA-encoded library (DEL) screening have created bioactivity datasets containing billions of molecules, unlocking new opportunities for machine learning (ML) in drug discovery. However, most ultra-large DEL libraries are…
View article: Structural basis of TMPRSS11D specificity and autocleavage activation
Structural basis of TMPRSS11D specificity and autocleavage activation Open
Transmembrane Protease, Serine-2 (TMPRSS2) and TMPRSS11D are human proteases that enable SARS-CoV-2 and Influenza A/B virus infections, but their biochemical mechanisms for facilitating viral cell entry remain unclear. We demonstrate these…
View article: An Adenosine Analogue Library Reveals Insights into Active Sites of Protein Arginine Methyltransferases and Enables the Discovery of a Selective PRMT4 Inhibitor
An Adenosine Analogue Library Reveals Insights into Active Sites of Protein Arginine Methyltransferases and Enables the Discovery of a Selective PRMT4 Inhibitor Open
Protein arginine methyltransferases (PRMTs) represent promising drug targets. However, the lack of isoform-selective chemical probes poses a significant hurdle in deciphering their biological roles. To address this issue, we devised a libr…
View article: H3K14ac facilitates the reinstallation of constitutive heterochromatin in <i>Drosophila</i> early embryos by engaging Eggless/SetDB1
H3K14ac facilitates the reinstallation of constitutive heterochromatin in <i>Drosophila</i> early embryos by engaging Eggless/SetDB1 Open
Constitutive heterochromatin, a fundamental feature of eukaryotic nucleus essential for transposon silencing and genome stability, is rebuilt on various types of repetitive DNA in the zygotic genome during early embryogenesis. However, the…
View article: A ligand discovery toolbox for the WWE domain family of human E3 ligases
A ligand discovery toolbox for the WWE domain family of human E3 ligases Open
The WWE domain is a relatively under-researched domain found in twelve human proteins and characterized by a conserved tryptophan-tryptophan-glutamate (WWE) sequence motif. Six of these WWE domain-containing proteins also contain domains w…
View article: The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition
The co-crystal structure of Cbl-b and a small-molecule inhibitor reveals the mechanism of Cbl-b inhibition Open
Cbl-b is a RING-type E3 ubiquitin ligase that is expressed in several immune cell lineages, where it negatively regulates the activity of immune cells. Cbl-b has specifically been identified as an attractive target for cancer immunotherapy…
View article: Early Embryonic Establishment of Constitutive Heterochromatin Involves H3K14ac-mediated Recruitment of Eggless/SetDB1
Early Embryonic Establishment of Constitutive Heterochromatin Involves H3K14ac-mediated Recruitment of Eggless/SetDB1 Open
SUMMARY Constitutive heterochromatin, built on various types of repetitive DNA, is a fundamental feature of eukaryotic nucleus essential for transposon silencing and genome stability. However, the molecular programs driving its de novo est…
View article: Discovery of a First-in-Class Small-Molecule Ligand for WDR91 Using DNA-Encoded Chemical Library Selection Followed by Machine Learning
Discovery of a First-in-Class Small-Molecule Ligand for WDR91 Using DNA-Encoded Chemical Library Selection Followed by Machine Learning Open
WD40 repeat-containing protein 91 (WDR91) regulates early-to-late endosome conversion and plays vital roles in endosome fusion, recycling, and transport. WDR91 was recently identified as a potential host factor for viral infection. We empl…
View article: Chemical Tools for the Gid4 Subunit of the Human E3 Ligase C-terminal to LisH (CTLH) Degradation Complex
Chemical Tools for the Gid4 Subunit of the Human E3 Ligase C-terminal to LisH (CTLH) Degradation Complex Open
We have developed a novel chemical handle (PFI-E3H1) and a chemical probe (PFI-7) as ligands for the Gid4 subunit of the human E3 ligase CTLH degradation complex. Through an efficient initial hit-ID campaign, structure-based drug design (S…
View article: Discovery of a 53BP1 Small Molecule Antagonist Using a Focused DNA-Encoded Library Screen
Discovery of a 53BP1 Small Molecule Antagonist Using a Focused DNA-Encoded Library Screen Open
Methyl-lysine reader p53 binding protein 1 (53BP1) is a central mediator of DNA break repair and is associated with various human diseases, including cancer. Thus, high-quality 53BP1 chemical probes can aid in further understanding the rol…
View article: <i>Cdyl</i> Deficiency Brakes Neuronal Excitability and Nociception through Promoting <i>Kcnb1</i> Transcription in Peripheral Sensory Neurons
<i>Cdyl</i> Deficiency Brakes Neuronal Excitability and Nociception through Promoting <i>Kcnb1</i> Transcription in Peripheral Sensory Neurons Open
Adv. Sci. 2022, 9, 2104317 DOI: 10.1002/advs.202104317 In the original published article the structure of the chemical compound reported in Figure 7a is incorrect. Please find the correct Figure 7 below.
View article: Discovery of a first-in-class small molecule ligand for WDR91 using DNA-encoded chemical library selection followed by machine learning
Discovery of a first-in-class small molecule ligand for WDR91 using DNA-encoded chemical library selection followed by machine learning Open
WD40 repeat-containing protein 91 regulates endosomal phosphatidylinositol 3-phosphate levels at the critical stage of endosome maturation and plays vital roles in endosome fusion, recycling, and transport by mediating protein-protein inte…
View article: A unique binding pocket induced by a noncanonical SAH mimic to develop potent and selective PRMT inhibitors
A unique binding pocket induced by a noncanonical SAH mimic to develop potent and selective PRMT inhibitors Open
Protein arginine methyltransferases (PRMTs) are attractive targets for developing therapeutic agents, but selective PRMT inhibitors targeting the cofactor SAM binding site are limited. Herein, we report the discovery of a noncanonical but …
View article: Discovery of a Novel DCAF1 Ligand Using a Drug–Target Interaction Prediction Model: Generalizing Machine Learning to New Drug Targets
Discovery of a Novel DCAF1 Ligand Using a Drug–Target Interaction Prediction Model: Generalizing Machine Learning to New Drug Targets Open
DCAF1 functions as a substrate recruitment subunit for the RING-type CRL4DCAF1 and the HECT family EDVPDCAF1 E3 ubiquitin ligases. The WDR domain of DCAF1 serves as a binding platform for substrate proteins and is als…
View article: Probing the mechanism of Cbl-b inhibition by a small-molecule inhibitor
Probing the mechanism of Cbl-b inhibition by a small-molecule inhibitor Open
Cbl-b is a RING-type E3 ubiquitin ligase that is expressed in several immune cell lineages, where it negatively regulates the activity of immune cells. Cbl-b has specifically been identified as an attractive target for cancer immunotherapy…
View article: Discovery of Nanomolar DCAF1 Small Molecule Ligands
Discovery of Nanomolar DCAF1 Small Molecule Ligands Open
DCAF1 is a substrate receptor of two distinct E3 ligases (CRL4DCAF1 and EDVP), plays a critical physiological role in protein degradation, and is considered a drug target for various cancers. Antagonists of DCAF1 could be used t…
View article: From study abroad to study at home: Spontaneous neuronal activity predicts depressive symptoms in overseas students during the COVID-19 pandemic
From study abroad to study at home: Spontaneous neuronal activity predicts depressive symptoms in overseas students during the COVID-19 pandemic Open
The objective of this study was to evaluate symptoms of depression and anxiety as well as changes in spontaneous neuronal activity in college students studying abroad during the coronavirus 2019 (COVID-19) pandemic. We examined functional …
View article: Caltubin regulates microtubule stability via Ca<sup>2+</sup>-dependent mechanisms favouring neurite regrowth
Caltubin regulates microtubule stability via Ca<sup>2+</sup>-dependent mechanisms favouring neurite regrowth Open
Microtubule regulation is highly controlled in nerve regeneration. Caltubin, a novel Lymnaea stagnalis protein, contains putative EF-hand calcium-binding motifs and promotes neuronal outgrowth in Lymnaea and mouse. Here, we generated cell-…
View article: A chemical probe to modulate human GID4 Pro/N-degron interactions
A chemical probe to modulate human GID4 Pro/N-degron interactions Open
The CTLH complex is a multi-subunit ubiquitin ligase complex that recognizes substrates with Pro/N-degrons via the substrate receptor GID4. Recently, focus has turned to this complex as a potential mediator of targeted protein degradation,…
View article: <i>Cdyl</i> Deficiency Brakes Neuronal Excitability and Nociception through Promoting <i>Kcnb1</i> Transcription in Peripheral Sensory Neurons
<i>Cdyl</i> Deficiency Brakes Neuronal Excitability and Nociception through Promoting <i>Kcnb1</i> Transcription in Peripheral Sensory Neurons Open
Epigenetic modifications are involved in the onset, development, and maintenance of pain; however, the precise epigenetic mechanism underlying pain regulation remains elusive. Here it is reported that the epigenetic factor chromodomain Y‐l…
View article: Survival‑related DLEU1 is associated with HPV infection status and serves as a biomarker in HPV‑infected cervical cancer
Survival‑related DLEU1 is associated with HPV infection status and serves as a biomarker in HPV‑infected cervical cancer Open
Human papillomavirus (HPV) is the most common risk factor for the occurrence of cervical cancer (CC). In recent years, the important roles of long non‑coding RNAs (lncRNAs) in CC have emerged, but studies on the relationship between lncRNA…
View article: Discovery of small molecule antagonists of human Retinoblastoma Binding Protein 4 (RBBP4)
Discovery of small molecule antagonists of human Retinoblastoma Binding Protein 4 (RBBP4) Open
RBBP4 is a nuclear WD40 motif-containing protein widely implicated in various cancers and a putative drug target. It interacts with multiple proteins within diverse complexes such as nucleosome remodeling and deacetylase (NuRD) complex and…
View article: Structural basis for the recognition of the S2, S5‐phosphorylated RNA polymerase II CTD by the mRNA anti‐terminator protein hSCAF4
Structural basis for the recognition of the S2, S5‐phosphorylated RNA polymerase II CTD by the mRNA anti‐terminator protein hSCAF4 Open
The C‐terminal domain (CTD) of RNA polymerase II serves as a binding platform for numerous enzymes and transcription factors involved in nascent RNA processing and the transcription cycle. The S2, S5‐phosphorylated CTD is recognized by the…
View article: A chemical probe targeting the PWWP domain alters NSD2 nucleolar localization
A chemical probe targeting the PWWP domain alters NSD2 nucleolar localization Open
View article: Structural basis of the TAM domain of BAZ2A in binding to DNA or RNA independent of methylation status
Structural basis of the TAM domain of BAZ2A in binding to DNA or RNA independent of methylation status Open
Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) (also called transcription termination factor-1 interacting protein 5), a key component of the nucleolar remodeling complex, recruits the nucleolar remodeling complex to ribosom…
View article: Structure–Activity Relationship of USP5 Inhibitors
Structure–Activity Relationship of USP5 Inhibitors Open
USP5 is a deubiquitinase that has been implicated in a range of diseases, including cancer, but no USP5-targeting chemical probe has been reported to date. Here, we present the progression of a chemical series that occupies the C-terminal …