Nicholas A. Till
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View article: The molecular mechanism of uptake and cell-to-cell transmission of arginine-containing dipeptide repeat proteins
The molecular mechanism of uptake and cell-to-cell transmission of arginine-containing dipeptide repeat proteins Open
Micro-satellite repeat expansion of the 5’ GGGGCC 3’ sequence in the C9orf72 gene is the most common monogenic form of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) translated from …
View article: Mapping the nanoscale organization of the human cell surface proteome reveals new functional associations and surface antigen clusters
Mapping the nanoscale organization of the human cell surface proteome reveals new functional associations and surface antigen clusters Open
The cell surface is a dynamic interface that controls cell-cell communication and signal transduction relevant to organ development, homeostasis and repair, immune reactivity, and pathologies driven by aberrant cell surface phenotypes. The…
View article: Trogocytosis targeting chimeras (TrogoTACs) for targeted protein transfer
Trogocytosis targeting chimeras (TrogoTACs) for targeted protein transfer Open
Cell surface proteins contribute to cellular identity and mediate a myriad of pathological and normal physiological processes. Multiple induced proximity strategies have emerged to manipulate the cell surface proteome, wherein a protein of…
View article: Tumor Immune Cell Targeting Chimeras (TICTACs) For Targeted Depletion of Macrophage-Associated Checkpoint Receptors
Tumor Immune Cell Targeting Chimeras (TICTACs) For Targeted Depletion of Macrophage-Associated Checkpoint Receptors Open
Immune cells in the tumor microenvironment are not only powerful regulators of immunosuppression and tumorigenesis, but also represent a dominant cell type, with tumor-associated macrophages (TAMs) comprising up to 50% of total cell mass i…
View article: The modified RNA base acp3U is an attachment site for N-glycans in glycoRNA
The modified RNA base acp3U is an attachment site for N-glycans in glycoRNA Open
We recently identified glycoRNA—a previously undescribed glycoconjugate—which consists of RNAs modified with secretory N-glycans and presented on the cell surface. While previous work supported a covalent linkage between RNA and glycans, t…
View article: 1178 Tumor-immune cell targeting chimeras (TICTACs): targeted immune reprogramming of the tumor microenvironment
1178 Tumor-immune cell targeting chimeras (TICTACs): targeted immune reprogramming of the tumor microenvironment Open
Background The immune cells in the tumor microenvironment (TME) are not only powerful regulators of immunosuppression and tumorigenesis, but also represent a dominant cell type, with tumor-associated macrophages (TAMs) comprising up to 50%…
View article: Photochemical Identification of Auxiliary Severe Acute Respiratory Syndrome Coronavirus 2 Host Entry Factors Using μMap
Photochemical Identification of Auxiliary Severe Acute Respiratory Syndrome Coronavirus 2 Host Entry Factors Using μMap Open
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of the COVID-19 pandemic, remains a global medical problem. Angiotensin-converting enzyme 2 (ACE2) was identified as the primary viral entry receptor…
View article: Searching for an ideal SERM: Mining tamoxifen structure–activity relationships
Searching for an ideal SERM: Mining tamoxifen structure–activity relationships Open
The repurposing of old drugs for new treatments has recently garnered increased attention in the face of new diseases and declining productivity of the pharmaceutial industry. This report draws attention to potential opportunities hiding i…
View article: The Application of Pulse Radiolysis to the Study of Ni(I) Intermediates in Ni-Catalyzed Cross-Coupling Reactions
The Application of Pulse Radiolysis to the Study of Ni(I) Intermediates in Ni-Catalyzed Cross-Coupling Reactions Open
Here we report the use of pulse radiolysis and spectroelectrochemistry to generate low-valent nickel intermediates relevant to synthetically important Ni-catalyzed cross-coupling reactions and interrogate their reactivities toward compropo…
View article: CCDC 1989188: Experimental Crystal Structure Determination
CCDC 1989188: Experimental Crystal Structure Determination Open
View article: CCDC 1914025: Experimental Crystal Structure Determination
CCDC 1914025: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: CCDC 1914024: Experimental Crystal Structure Determination
CCDC 1914024: Experimental Crystal Structure Determination Open
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available …
View article: Mechanistic Analysis of Metallaphotoredox C–N Coupling: Photocatalysis Initiates and Perpetuates Ni(I)/Ni(III) Coupling Activity
Mechanistic Analysis of Metallaphotoredox C–N Coupling: Photocatalysis Initiates and Perpetuates Ni(I)/Ni(III) Coupling Activity Open
The combined use of reaction kinetic analysis, ultrafast spectroscopy, and stoichiometric organometallic studies has enabled the elucidation of the mechanistic underpinnings to a photocatalytic C-N cross-coupling reaction. Steady-state and…
View article: Discovery of an Atropisomeric PI3Kβ Selective Inhibitor through Optimization of the Hinge Binding Motif
Discovery of an Atropisomeric PI3Kβ Selective Inhibitor through Optimization of the Hinge Binding Motif Open
A series of PI3Kβ selective inhibitors derived from a novel 4-(1H-benzo[d]imidazol-1-yl)quinoline chemotype has been rationally designed. Crucial to achieving the desired selectivity over the other class I PI3K isoforms, including the chal…
View article: Transient Absorption Spectroscopy Offers Mechanistic Insights for an Iridium/Nickel-Catalyzed C–O Coupling
Transient Absorption Spectroscopy Offers Mechanistic Insights for an Iridium/Nickel-Catalyzed C–O Coupling Open
We report mechanistic insights into an iridium/nickel photocatalytic C-O cross-coupling reaction from time-resolved spectroscopic studies. Using transient absorption spectroscopy, energy transfer from an iridium photocatalyst to a catalyti…
View article: Atropisomerism by Design: Discovery of a Selective and Stable Phosphoinositide 3-Kinase (PI3K) β Inhibitor
Atropisomerism by Design: Discovery of a Selective and Stable Phosphoinositide 3-Kinase (PI3K) β Inhibitor Open
Atropisomerism is a type of axial chirality in which enantiomers or diastereoisomers arise due to hindered rotation around a bond axis. In this manuscript, we report a case in which torsional scan studies guided the thoughtful creation of …
View article: Decarboxylative Hydroalkylation of Alkynes
Decarboxylative Hydroalkylation of Alkynes Open
The merger of open- and closed-shell elementary organometallic steps has enabled the selective intermolecular addition of nucleophilic radicals to unactivated alkynes. A range of carboxylic acids can be subjected to a CO(2) extrusion, nick…