Physiology, Cellular and Molecular Neuroscience, Pharmacology, Biophysics
280
Scopus Publications
20911
Scholar Citations
79
Scholar h-index
255
Scholar i10-index
Scopus Publications
Cyclization of the Analgesic α-Conotoxin Vc1.1 With a Non-Natural Linker: Effects on Structure, Stability, and Bioactivity Yuhui Zhang, Han Shen Tae, David J. Adams, Thomas Durek, David J. Craik Journal of Peptide Science, 2025 α‐Conotoxin Vc1.1 is a disulfide‐rich peptide and a promising drug candidate for treating neuropathic and chronic pain. Backbone cyclization was applied to enhance its drug‐like properties, resulting in improved serum stability and oral bioavailability. However, this modification also adversely affected its stability and activity in simulated intestinal fluid (SIF). To address these adverse effects, we explored the use of polyethylene glycol (PEG) linkers as substitutes for peptide backbone cyclization linkers. PEG linkers are smaller, more flexible, and more stable than peptide linkers. Furthermore, previous studies have demonstrated that PEG backbone linkers can enhance the activity of conotoxins. In this study, we synthesized four PEG‐backboned cyclic Vc1.1 (cVc1.1) analogues with varying lengths of PEG linkers and used a chemo‐enzymatic method to cyclize these analogues. Their structure, stability, and activity were subsequently evaluated. Although the results revealed that PEG linkers preserved the SIF stability and activity of cVc1.1, they highlighted the crucial role of the peptide's helical structure in maintaining its stability and activity. Additionally, this work introduces a novel approach for synthesizing cyclic conotoxins.
Neural control of the heart: intrinsic cardiac ganglion neurons David J. Adams Journal of Physiology, 2025 The mammalian intrinsic cardiac nervous system comprises clusters of parasympathetic postganglionic efferent neurons, local interneurons, and afferent neurons dispersed throughout the atrial epicardium and interatrial septum of the heart. These intracardiac ganglia receive excitatory cholinergic innervation from preganglionic parasympathetic (vagal) fibres and are also innervated by sympathetic postganglionic nerve fibres, as well as afferent fibres from dorsal root and nodose (vagal) sensory ganglia. Together, neurons within these ganglia form a complex neural network characterised by neurochemical diversity, suggesting a level of functional sophistication beyond a simple relay station (Adams et al., 2022; Ardell & Armour, 2016; Herring et al., 2019). The diverse functional and neurochemical properties of these intracardiac neurons and their strategic location provide the final site of neural control in the heart, mediating local reflex responses to changes in cardiac performance or environmental factors within the myocardium such as those induced by ischaemia. Importantly, the final discharge pattern of these neurons regulates chronotropic and dromotropic elements of cardiac function. In this issue of The Journal of Physiology, Tompkins et al. (2025) present a detailed comparative analysis of intrinsic cardiac neurons (ICNs) across three species – mouse, pig, and human – using a multidisciplinary approach. A comprehensive atlas that highlights both similarities and differences in ICN structure and function among these species is presented. This resource enhances our understanding of ICNs in cardiac physiology and provides a basis for future research in cardiac neural control and potential therapeutic strategies. A key strength of the study is its methodical approach to characterizing ICNs from multiple perspectives: histochemical, ultrastructural, and neurophysiological. Immunohistochemistry and electron microscopy reveal details of ganglionic composition, neuropeptide expression and synaptic morphology, illustrating notable interspecies differences. For example, human ICNs show prominent vasoactive intestinal peptide immunoreactivity, distinguishing them from those in pigs and mice. This finding suggests that species-specific variations in neuropeptide expression may influence ICN function and modulation, an important consideration for translating animal research to human models. The comparison of synaptic function across species uncovers notable differences in synaptic efficacy and integration. In particular, it is observed that mouse ICNs, lacking dendrites, form axosomatic connections with high synaptic efficacy, sustaining high-fidelity neurotransmission. In contrast, pig ICNs possess extensive dendritic arbours, supporting greater integration of synaptic inputs, aligning with larger animals' physiological demands. These observations, akin to those for sympathetic ganglion neurons, emphasize the importance of dendritic architecture in ICN function, suggesting that neuronal morphology may influence the integrative capabilities of ICNs and, ultimately, their role in cardiac regulation across species. Additionally, the authors provide a compelling analysis of electrophysiological characteristics, noting significant differences in excitability between species. Human ICNs exhibit larger after-hyperpolarizations following the somatic action potential compared with those in mouse and pig, which may indicate distinct regulatory mechanisms in human cardiac autonomic function. The finding that the firing pattern of human ICNs is predominantly tonic while pig ICNs are phasic, with mouse ICNs displaying both phenotypes, suggests a potential evolution of excitability properties that aligns with the functional complexity of cardiac control in larger mammals. Changes in parasympathetic tone within intracardiac neurons are linked to increased risk of arrhythmias, heart failure and mortality. Exploratory clinical studies have shown that the activity of the intracardiac nervous system can predispose patients to paroxysmal atrial arrhythmias. Specifically, intracardiac neurons play a critical role in the development and propagation of atrial fibrillation (Ashton et al., 2025), a common cardiac arrhythmia characterised by irregular, rapid atrial contractions that disrupt the atrial function. The study by Tompkins et al. (2025) provides valuable insights into the translational relevance of its findings. By comparing ICN characteristics across species, it highlights the advantages and limitations of these animal models for studying human cardiac physiology. Notably, the study recognises mice as a valuable model for genetic manipulation, while highlighting pigs as closer physiological analogues to humans. This comparative approach could greatly benefit the development of neuromodulation therapies targeting cardiac autonomic dysfunction, as it allows for a better understanding of how animal models may or may not replicate human ICN function. However, the paper could have benefited from a more detailed discussion of potential clinical applications. While the authors briefly address neuromodulation techniques, elaborating on how their findings might inform or refine these approaches would add valuable context. Insights into unique excitability profiles and neuropeptide distributions of human ICNs could guide the development of targeted strategies for specific ICN populations, especially in treating dysregulated autonomic conditions, such as arrhythmias or heart failure. Overall, this paper represents a significant contribution to our understanding of intrinsic cardiac neurons, providing a thorough, well-structured analysis that highlights the complexity and evolutionary diversity of ICNs. While further studies are needed to translate these findings into clinical applications, this work lays a solid foundation for future exploration of the neurophysiological and neurochemical properties of intracardiac neurons. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. None declared. Sole author. None.
Molecular determinants of the selectivity and potency of α-conotoxin Vc1.1 for human nicotinic acetylcholine receptors Han-Shen Tae, Andrew Hung, Richard J. Clark, David J. Adams Journal of Biological Chemistry, 2025 The α-conotoxins (α-Ctxs) are short, disulfide-rich peptides derived from the venom of the Conus marine snails, primarily acting as antagonists of nicotinic acetylcholine receptors (nAChRs). Specifically, α-Ctx Vc1.1, a 16-amino acid peptide from Conus victoriae , competitively antagonizes non-muscle nAChRs, inhibits nicotine-induced currents in bovine chromaffin cells, and alleviates neuropathic pain in rat models. Although Vc1.1 selectively inhibits rat α9α10 nAChRs, its potency and selectivity across human nAChR subtypes remain unresolved. In this study, we assessed the activity of Vc1.1 on human (h) nAChRs heterologously expressed in Xenopus laevis oocytes using the two-electrode voltage clamp technique and simulated interactions using computational modeling. Vc1.1 selectively antagonized homomeric α9 and heteromeric α3β2 nAChRs, with half-maximal inhibitory concentrations (IC 50 ) of 160 nM and 232 nM, respectively. At hα9[N179A]α10, Vc1.1 exhibited a 20-fold decrease in potency compared to hα9α10, due to the loss of hydrogen bonding with Vc1.1-D11. Conversely, Vc1.1 was four-fold more potent at hα3β2[E86A] compared to hα3β2, possibly influenced by the proximal residue β2-K104, as suggested by molecular dynamics (MD) simulations. Additionally, Vc1.1's potency doubled at hα9[N213K]α10, whereas it remained unchanged at hα9[N213R]α10 nAChRs. MD simulations indicate that altered interactions between the mutant hα9 N179A, N213K, and N213R side chains and Vc1.1-D5 may partly explain these changes in potency. The inhibitory action of Vc1.1 at α9-containing nAChRs is particularly relevant given their role in neuroinflammation, presenting a potential therapeutic pathway for alleviating neuropathic and inflammatory pain. This study provides valuable insights into the rational design of Vc1.1-derived α-Ctxs with enhanced nAChR subtype selectivity.
GABAB Receptor Modulation of Membrane Excitability in Human Pluripotent Stem Cell-Derived Sensory Neurons by Baclofen and α-Conotoxin Vc1.1 Mitchell St Clair‐Glover, Arsalan Yousuf, Dominic Kaul, Mirella Dottori, David J. Adams Journal of Neurochemistry, 2025 GABA B receptor (GABA B R) activation is known to alleviate pain by reducing neuronal excitability, primarily through inhibition of high voltage‐activated (HVA) calcium (Ca V 2.2) channels and potentiating G protein–coupled inwardly rectifying potassium (GIRK) channels. Although the analgesic properties of small molecules and peptides have been primarily tested on isolated murine dorsal root ganglion (DRG) neurons, emerging strategies to develop, study, and characterise human pluripotent stem cell (hPSC)‐derived sensory neurons present a promising alternative. In this study, hPSCs were efficiently differentiated into peripheral DRG‐induced sensory neurons (iSNs) using a combined chemical and transcription factor‐driven approach via a neural crest cell intermediate. Molecular characterisation and transcriptomic analysis confirmed the expression of key DRG markers such as BRN3A, ISLET1, and PRPH, in addition to GABA B R and ion channels including Ca V 2.2 and GIRK1 in iSNs. Functional characterisation of GABA B R was conducted using whole‐cell patch clamp electrophysiology, assessing neuronal excitability under current‐clamp conditions in the absence and presence of GABA B R agonists baclofen and α‐conotoxin Vc1.1. Both baclofen (100 μM) and Vc1.1 (1 μM) significantly reduced membrane excitability by hyperpolarising the resting membrane potential and increasing the rheobase for action potential firing. In voltage‐clamp mode, baclofen and Vc1.1 inhibited HVA Ca 2+ channel currents, which were attenuated by the selective GABA B R antagonist CGP 55845. However, modulation of GIRK channels by GABA B Rs was not observed in the presence of baclofen or Vc1.1, suggesting that functional GIRK1/2 channels were not coupled to GABA B Rs in hPSC‐derived iSNs. This study is the first to report GABA B R modulation of membrane excitability in iSNs by baclofen and Vc1.1, highlighting their potential as a future model for studying analgesic compounds. image
Development of an Intravenously Stable Disulfide-Rich Peptide for the Treatment of Chemotherapy-Induced Neuropathic Pain Tianmiao Li, Han-Shen Tae, Shen Chen, Xiao Li, Jiazhen Liang, Teng Pan, Zixuan Zhang, Tao Jiang, David J. Adams, Rilei Yu Journal of Medicinal Chemistry, 2024 α-conotoxins (α-Ctxs), a class of disulfide-rich conopetides, are excellent drug leads due to their small size, high selectivity, and potency for specific membrane receptors and ion channels involved in pain transmission. However, their high susceptibility to proteolytic degradation limits their therapeutic potential. In this study, we designed and synthesized a series of conformationally stable analogues of α-Ctx Mr1.1[S4Dap] using various structural optimization strategies. The Mr1.1[S4Dap, C16Pen] analogue maintained potency at human α9α10 nicotinic acetylcholine receptors, with a half-maximal inhibitory concentration (IC 50 ) of 4 nM. It exhibited over a 5-fold increase in serum stability compared to Mr1.1[S4Dap], without disrupting its overall conformation. Furthermore, intravenous application of Mr1.1[S4Dap, C16Pen] showed potent analgesic activity in oxaliplatin-induced cold allodynia, indicating a high potential for drug development. Overall, the results from this study provide valuable insights for optimizing the serum stability of disulfide-rich peptides in future therapeutic applications.
Tabernanthalog and ibogainalog inhibit the α7 and α9α10 nicotinic acetylcholine receptors via different mechanisms and with higher potency than the GABAA receptor and CaV2.2 channel Han-Shen Tae, Marcelo O. Ortells, Arsalan Yousuf, Sophia Q. Xu, Gustav Akk, David J. Adams, Hugo R. Arias Biochemical Pharmacology, 2024 In this study, we have investigated the pharmacological activity and structural interaction of two novel psychoplastogens, tabernanthalog (TBG) and ibogainalog (IBG) at heterologously-expressed rat (r) and human (h) nicotinic acetylcholine receptors (nAChRs), the rα1β2γ2L γ-aminobutyric acid type A receptor (GABAAR), and the human voltage-gated N-type calcium channel (CaV2.2 channel). Both compounds inhibited the nAChRs with the following receptor selectivity: α9α10 > α7 > α3β2 ≅ α3β4, indicating that β2/β4 subunits are relatively less important for their activity. The potencies of TBG and IBG were comparable at hα7 and hα9α10 subtypes, and comparable to their rat counterparts. TBG- and IBG-induced inhibition of rα7 was ACh concentration-independent and voltage-dependent, whereas rα9α10 inhibition was ACh concentration-dependent and voltage-independent, suggesting that they interact with the α7 ion channel pore and α9α10 orthosteric ligand binding site, respectively. These results were supported by molecular docking studies showing that at the α7 model TBG forms stable interactions with luminal rings at 9′, 13′, and 16′, whereas IBG mostly interacts with the extracellular-transmembrane junction. In the α9α10 model, however, these compounds interacted with several residues from the principal (+) and complementary (–) sides in the transmitter binding site. Ibogaminalog (DM506) also interacted with a non-luminal site at α7, and one α9α10 orthosteric site. TBG and IBG inhibited the GABAAR and CaV2.2 channels with 10 to 30-fold lower potencies. In sum, we show that TBG and IBG inhibit the α7 and α9α10 nAChRs by noncompetitive and competitive mechanisms, respectively, and with higher potency than the GABAAR and CaV2.2 channel.
Rational Design of Potent α-Conotoxin PeIA Analogues with Non-Natural Amino Acids for the Inhibition of Human α9α10 Nicotinic Acetylcholine Receptors Tianmiao Li, Han-Shen Tae, Jiazhen Liang, Zixuan Zhang, Xiao Li, Tao Jiang, David J. Adams, Rilei Yu Marine Drugs, 2024 α-Conotoxins (α-CTxs) are structurally related peptides that antagonize nicotinic acetylcholine receptors (nAChRs), which may serve as new alternatives to opioid-based treatment for pain-related conditions. The non-natural amino acid analogues of α-CTxs have been demonstrated with improved potency compared to the native peptide. In this study, we chemically synthesized Dab/Dap-substituted analogues of α-CTx PeIA and evaluated their activity at heterologously expressed human α9α10 nAChRs. PeIA[S4Dap, S9Dap] had the most potent half-maximal inhibitory concentration (IC50) of 0.93 nM. Molecular dynamic simulations suggested that the side chain amino group of Dap4 formed additional hydrogen bonds with S168 and D169 of the receptor and Dap9 formed an extra hydrogen bond interaction with Q34, which is distinctive to PeIA. Overall, our findings provide new insights into further development of more potent analogues of α-CTxs, and PeIA[S4Dap, S9Dap] has potential as a drug candidate for the treatment of chronic neuropathic pain.
Dual Antagonism of α9α10 nAChR and GABAB Receptor-Coupled CaV2.2 Channels by an Analgesic αO-Conotoxin Analogue Xiao Li, Han-Shen Tae, Shen Chen, Arsalan Yousuf, Linhong Huang, Jinghui Zhang, Tao Jiang, David J. Adams, Rilei Yu Journal of Medicinal Chemistry, 2024 Pain severely affects the physical and mental health of patients. The need to develop nonopioid analgesic drugs to meet medical demands is urgent. In this study, we designed a truncated analogue of αO-conotoxin, named GeX-2, based on disulfide-bond deletion and sequence truncation. GeX-2 retained the potency of its parent peptide at the human α9α10 nAChR and exhibited potent inhibitory activity at CaV2.2 channels via activation of the GABAB receptor (GABABR). Importantly, GeX-2 significantly alleviated pain in the rat model of chronic constriction injury. The dual inhibition of GeX-2 at both α9α10 nAChRs and CaV2.2 channels is speculated to synergistically mediate the potent analgesic effects. Results from site-directed mutagenesis assay and computational modeling suggest that GeX-2 preferentially interacts with the α10(+)α10(-) binding site of α9α10 nAChR and favorably binds to the top region of the GABABR2 subunit. The study offers vital insights into the molecular action mechanism of GeX-2, demonstrating its potential as a novel nonopioid analgesic.
The Antinociceptive Activity of (E)-3-(thiophen-2-yl)- N -(p-tolyl)acrylamide in Mice Is Reduced by (E)-3-(furan-2-yl)- N -methyl- N -(p-tolyl)acrylamide Through Opposing Modulatory Mechanisms at the α7 Nicotinic Acetylcholine Receptor Hugo R. Arias, Han-Shen Tae, Laura Micheli, Arsalan Yousuf, Dina Manetti, Maria Novella Romanelli, Carla Ghelardini, David J. Adams, Lorenzo Di Cesare Mannelli Anesthesia and Analgesia, 2023 BACKGROUND: The primary objective of this study was to characterize the pharmacological and behavioral activity of 2 novel compounds, DM497 [(E)-3-(thiophen-2-yl)-N-(p-tolyl)acrylamide] and DM490 [(E)-3-(furan-2-yl)-N-methyl-N-(p-tolyl)acrylamide], structural derivatives of PAM-2, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor (nAChR). METHODS: A mouse model of oxaliplatin-induced neuropathic pain (2.4 mg/kg, 10 injections) was used to test the pain-relieving properties of DM497 and DM490. To assess possible mechanisms of action, the activity of these compounds was determined at heterologously expressed α7 and α9α10 nAChRs, and voltage-gated N-type calcium channel (CaV2.2) using electrophysiological techniques. RESULTS: Cold plate tests indicated that 10 mg/kg DM497 was able to decrease neuropathic pain in mice induced by the chemotherapeutic agent oxaliplatin. In contrast, DM490 induced neither pro- nor antinociceptive activity but inhibited DM497’s effect at equivalent dose (30 mg/kg). These effects are not a product of changes in motor coordination or locomotor activity. At α7 nAChRs, DM497 potentiated whereas DM490 inhibited its activity. In addition, DM490 antagonized the α9α10 nAChR with >8-fold higher potency than that for DM497. In contrast, DM497 and DM490 had minimal inhibitory activity at the CaV2.2 channel. Considering that DM497 did not increase the mouse exploratory activity, an indirect anxiolytic mechanism was not responsible for the observed antineuropathic effect. CONCLUSIONS: The antinociceptive activity of DM497 and the concomitant inhibitory effect of DM490 are mediated by opposing modulatory mechanisms on the α7 nAChR, whereas the involvement of other possible nociception targets such as the α9α10 nAChR and CaV2.2 channel can be ruled out.
A previously unrecognized superfamily of macro-conotoxins includes an inhibitor of the sensory neuron calcium channel Cav2.3 Celeste M. Hackney, Paula Flórez Salcedo, Emilie Mueller, Thomas Lund Koch, Lau D. Kjelgaard, Maren Watkins, Linda G. Zachariassen, Pernille Sønderby Tuelung, Jeffrey R. McArthur, David J. Adams, Anders S. Kristensen, Baldomero Olivera, Rocio K. Finol-Urdaneta, Helena Safavi-Hemami, Jens Preben Morth, Lars Ellgaard Plos Biology, 2023 Animal venom peptides represent valuable compounds for biomedical exploration. The venoms of marine cone snails constitute a particularly rich source of peptide toxins, known as conotoxins. Here, we identify the sequence of an unusually large conotoxin, Mu8.1, which defines a new class of conotoxins evolutionarily related to the well-known con-ikot-ikots and 2 additional conotoxin classes not previously described. The crystal structure of recombinant Mu8.1 displays a saposin-like fold and shows structural similarity with con-ikot-ikot. Functional studies demonstrate that Mu8.1 curtails calcium influx in defined classes of murine somatosensory dorsal root ganglion (DRG) neurons. When tested on a variety of recombinantly expressed voltage-gated ion channels, Mu8.1 displayed the highest potency against the R-type (Cav2.3) calcium channel. Ca2+ signals from Mu8.1-sensitive DRG neurons were also inhibited by SNX-482, a known spider peptide modulator of Cav2.3 and voltage-gated K+ (Kv4) channels. Our findings highlight the potential of Mu8.1 as a molecular tool to identify and study neuronal subclasses expressing Cav2.3. Importantly, this multidisciplinary study showcases the potential of uncovering novel structures and bioactivities within the largely unexplored group of macro-conotoxins.
Investigation of CACNA1I Cav3.3 Dysfunction in Hemiplegic Migraine Neven Maksemous, Claire D. Blayney, Heidi G. Sutherland, Robert A. Smith, Rod A. Lea, Kim Ngan Tran, Omar Ibrahim, Jeffrey R. McArthur, Larisa M. Haupt, M. Zameel Cader, Rocio K. Finol-Urdaneta, David J. Adams, Lyn R. Griffiths Frontiers in Molecular Neuroscience, 2022
Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider Rocio K. Finol-Urdaneta, Rebekah Ziegman, Zoltan Dekan, Jeffrey R. McArthur, Stewart Heitmann, Karen Luna-Ramirez, Han-Shen Tae, Alexander Mueller, Hana Starobova, Yanni K.-Y. Chin, Joshua S. Wingerd, Eivind A. B. Undheim, Ben Cristofori-Armstrong, Adam P. Hill, Volker Herzig, Glenn F. King, Irina Vetter, Lachlan D. Rash, David J. Adams, Paul F. Alewood Proceedings of the National Academy of Sciences of the United States of America, 2022
Cardiac vagal ganglia David J. Adams, Jesse L. Ashton, Johanna M. Montgomery Primer on the Autonomic Nervous System Fourth Edition, 2022
Trends in peptide drug discovery Markus Muttenthaler, Glenn F. King, David J. Adams, Paul F. Alewood Nature Reviews Drug Discovery, 2021
Alkyne-Bridged α-Conotoxin Vc1.1 Potently Reverses Mechanical Allodynia in Neuropathic Pain Models Alessia Belgi, James V. Burnley, Christopher A. MacRaild, Sandeep Chhabra, Khaled A. Elnahriry, Samuel D. Robinson, Simon G. Gooding, Han-Shen Tae, Peter Bartels, Mahsa Sadeghi, Fei-Yue Zhao, Haifeng Wei, David Spanswick, David J. Adams, Raymond S. Norton, Andrea J. Robinson Journal of Medicinal Chemistry, 2021
Interaction of Synthetic Human SLURP-1 with the Nicotinic Acetylcholine Receptors Thomas Durek, Irina V. Shelukhina, Han-Shen Tae, Panumart Thongyoo, Ekaterina N. Spirova, Denis S. Kudryavtsev, Igor E. Kasheverov, Grazyna Faure, Pierre-Jean Corringer, David J. Craik, David J. Adams, Victor I. Tsetlin Scientific Reports, 2017
Purification of immature neuronal cells from neural stem cell progeny Hassan Azari, Geoffrey W. Osborne, Takahiro Yasuda, Mohammad G. Golmohammadi, Maryam Rahman, Loic P. Deleyrolle, Ebrahim Esfandiari, David J. Adams, Bjorn Scheffler, Dennis A. Steindler, Brent A. Reynolds Plos One, 2011
Allosteric α1-Adrenoreceptor Antagonism by the Conopeptide ρ-TIA Iain A. Sharpe, Linda Thomas, Marion Loughnan, Leonid Motin, Elka Palant, Daniel E. Croker, Dianne Alewood, Songhai Chen, Robert M. Graham, Paul F. Alewood, David J. Adams, Richard J. Lewis Journal of Biological Chemistry, 2003
Novel ω-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes Richard J. Lewis, Katherine J. Nielsen, David J. Craik, Marion L. Loughnan, Denise A. Adams, Iain A. Sharpe, Tudor Luchian, David J. Adams, Trudy Bond, Linda Thomas, Alun Jones, Jodi-Lea Matheson, Roger Drinkwater, Peter R. Andrews, Paul F. Alewood Journal of Biological Chemistry, 2000
Membrane potential and Na+-K+ pump activity modulate resting and bradykinin-stimulated changes in cytosolic free calcium in cultured endothelial cells from bovine atria Journal of Biological Chemistry, 1990
GABA B receptor‐mediated modulation of sensory neuron excitability: Roles of Ca V 2.2, G‐protein‐coupled inwardly rectifying potassium (GIRK) channels, and … M Brizuela, AR Bony, S Garcia‐Caraballo, DJ Adams, SM Brierley Experimental Physiology 111 (4), 2026-2043 , 2026 2026
A deep learning framework (CreoPep) for target-specific design and optimization of conotoxin peptides C Ge, HS Tae, L Lu, Z Zhang, Z Huang, B An, Y Wang, T Jiang, W Cai, ... Communications Chemistry , 2026 2026
Isodrimenine Derivatives Selectively Inhibit Human α7-Containing Nicotinic Acetylcholine Receptors via Negative Allosteric Modulation HS Tae, MO Ortells, A Ciocarlan, A Aricu, L Lungu, S Blaja, DJ Adams, ... ACS Chemical Neuroscience 17 (1), 260-274 , 2026 2026
Induced Proprioceptor and Low-Threshold Mechanoreceptor Neurons Derived from Human Pluripotent Stem Cells Exhibit Distinct Functional Mechanosensory Properties DM Hulme AJ, Finol-Urdaneta RK, McArthur JR, Marzano NR, Maksour S, Thind A ... Advanced Science , 2025 2025 Citations: 1
Dual Agonist/Antagonist Modulation of α9-Containing Nicotinic Acetylcholine Receptors by 2-Ammoniumethyl Ethers of Stilbenol and Stilbenol Analogues A Giraudo, HS Tae, A Hung, K Richter, B Shivankar, E Armano, V Grau, ... Journal of Medicinal Chemistry 68 (24), 26099-26120 , 2025 2025
Dual-Action Tetrapeptide Analogue of Psychrophilic Fungal Origin: Potent Inhibitor of Human Nicotinic Acetylcholine Receptors with Antinociceptive and Muscle-Relaxant Activity L Lu, HS Tae, C Ge, X Zhang, T Pan, Z Zhang, T Jiang, W Cai, DJ Adams, ... Journal of Medicinal Chemistry 68 (24), 26175-26187 , 2025 2025
Functional and structural interactions of novel acrylamide-based compounds with the α7 nicotinic acetylcholine receptor HS Tae, MO Ortells, KM Targowska-Duda, D Manetti, MN Romanelli, ... Biochemical Pharmacology, 117463 , 2025 2025
Spider venom peptides with unique fold selectively block Shaker-type potassium channels AI Kuzmenkov, VA Iunusova, VA Lushpa, YA Deyev, VV Babenko, ... Cellular and Molecular Life Sciences 82 (1), 300 , 2025 2025 Citations: 1
Erabutoxin mutants demonstrate interface selectivity at human fetal and adult muscle-type nicotinic acetylcholine receptors CYL Chan, HS Tae, CY Koh, DJ Adams, RM Kini Biochemical Pharmacology, 117189 , 2025 2025 Citations: 1
Cyclization of the Analgesic α‐Conotoxin Vc1. 1 With a Non‐Natural Linker: Effects on Structure, Stability, and Bioactivity Y Zhang, HS Tae, DJ Adams, T Durek, DJ Craik Journal of Peptide Science 31 (6), e70017 , 2025 2025 Citations: 2
Parkinson's disease‐linked Kir4. 2 mutation R28C leads to loss of ion channel function X Chen, RK Finol‐Urdaneta, M Chen, AM Sykes, B Gao, J Iqbal, ... The Journal of Physiology 603 (12), 3499-3518 , 2025 2025 Citations: 5
CreoPep: A Universal Deep Learning Framework for Target-Specific Peptide Design and Optimization C Ge, HS Tae, Z Zhang, L Lu, Z Huang, Y Wang, T Jiang, W Cai, S Chang, ... arXiv preprint arXiv:2505.02887 , 2025 2025 Citations: 4
Differential contributions of Ca V 2.2, GIRK, and HCN channel to the modulation of excitability by α-conotoxin Vc1.1 and baclofen in somatic and visceral sensory … M Brizuela, AR Bony, S Garcia Caraballo, DJ Adams, SM Brierley 2025
Contribution of Ca V 2.2 and GIRK1/2 channels to membrane excitability of rodent and human dorsal root ganglion neurons M Brizuela, AR Bony, SG Caraballo, DJ Adams, SM Brierley bioRxiv, 2025.03. 21.644483 , 2025 2025
GABA B Receptor Modulation of Membrane Excitability in Human Pluripotent Stem Cell‐Derived Sensory Neurons by Baclofen and α‐Conotoxin Vc1.1 M St Clair‐Glover, A Yousuf, D Kaul, M Dottori, DJ Adams Journal of Neurochemistry 169 (1), e70004 , 2025 2025 Citations: 2
Molecular determinants of the selectivity and potency of α-conotoxin Vc1. 1 for human nicotinic acetylcholine receptors HS Tae, A Hung, RJ Clark, DJ Adams Journal of Biological Chemistry 301 (1), 108017 , 2025 2025 Citations: 5
Neural control of the heart: intrinsic cardiac ganglion neurons. DJ Adams Journal of Physiology 603 (7), 1907-1908 , 2024 2024
Development of an intravenously stable disulfide-rich peptide for the treatment of chemotherapy-induced neuropathic pain T Li, HS Tae, S Chen, X Li, J Liang, T Pan, Z Zhang, T Jiang, DJ Adams, ... Journal of Medicinal Chemistry 67 (21), 18741-18752 , 2024 2024 Citations: 9
N-terminal capping of the αo-conotoxin analogue gex-2 improves the serum stability and selectivity toward the human α9α10 nicotinic acetylcholine receptor X Li, S Zhou, HS Tae, S Wang, T Li, W Cai, T Jiang, DJ Adams, R Yu Journal of Medicinal Chemistry 67 (20), 18400-18411 , 2024 2024 Citations: 7
Molecular determinants of the selectivity and potency of α-conotoxin Vc1. 1 for human nicotinic acetylcholine receptor subtypes HS Tae, A Hung, DJ Adams Toxicon 248, 107988 , 2024 2024
MOST CITED SCHOLAR PUBLICATIONS
Trends in peptide drug discovery M Muttenthaler, GF King, DJ Adams, PF Alewood Nature reviews Drug discovery 20 (4), 309-325 , 2021 2021 Citations: 2144
Ion channels and regulation of intracellular calcium in vascular endothelial cells DJ Adams, J Barakeh, R Laskey, C Van Breemen The FASEB Journal 3 (12), 2389-2400 , 1989 1989 Citations: 555
The permeability of the endplate channel to organic cations in frog muscle. TM Dwyer, DJ Adams, B Hille The Journal of general physiology 75 (5), 469-492 , 1980 1980 Citations: 449
The permeability of endplate channels to monovalent and divalent metal cations. DJ Adams, TM Dwyer, B Hille The Journal of general physiology 75 (5), 493-510 , 1980 1980 Citations: 415
IONIC CURRENTS* i isss IN MOLLUSCAN SOMA DJ Adams, SJ Smith, SN Thompson Ann. Are iVrtnwi 3, 141-67 , 1980 1980 Citations: 409
The engineering of an orally active conotoxin for the treatment of neuropathic pain RJ Clark, J Jensen, DJ Craik, ST Nevin, BP Callaghan, DJ Adams Angewandte Chemie International Edition 49 (37), 6545-6548 , 2010 2010 Citations: 394
Two new classes of conopeptides inhibit the α1-adrenoceptor and noradrenaline transporter IA Sharpe, J Gehrmann, ML Loughnan, L Thomas, DA Adams, A Atkins, ... Nature neuroscience 4 (9), 902-907 , 2001 2001 Citations: 310
Engineering stable peptide toxins by means of backbone cyclization: stabilization of the α-conotoxin MII RJ Clark, H Fischer, L Dempster, NL Daly, KJ Rosengren, ST Nevin, ... Proceedings of the National Academy of Sciences 102 (39), 13767-13772 , 2005 2005 Citations: 307
Novel ω-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes RJ Lewis, KJ Nielsen, DJ Craik, ML Loughnan, DA Adams, IA Sharpe, ... Journal of Biological Chemistry 275 (45), 35335-35344 , 2000 2000 Citations: 307
μO-conotoxin MrVIB selectively blocks Na v 1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits J Ekberg, A Jayamanne, CW Vaughan, S Aslan, L Thomas, J Mould, ... Proceedings of the National Academy of Sciences 103 (45), 17030-17035 , 2006 2006 Citations: 257
Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer H Kulhari, D Pooja, S Shrivastava, M Kuncha, VGM Naidu, V Bansal, ... Scientific reports 6 (1), 23179 , 2016 2016 Citations: 215
α-Selenoconotoxins, a new class of potent α7 neuronal nicotinic receptor antagonists CJ Armishaw, NL Daly, ST Nevin, DJ Adams, DJ Craik, PF Alewood Journal of Biological Chemistry 281 (20), 14136-14143 , 2006 2006 Citations: 213
Calcium entry through receptor-operated channels in bovine pulmonary artery endothelial cells A Johns, TW Lategan, NJ Lodge, US Ryan, C Van Breemen, DJ Adams Tissue and Cell 19 (6), 733-745 , 1987 1987 Citations: 213
Analgesic α-conotoxins Vc1. 1 and Rg1A inhibit N-type calcium channels in rat sensory neurons via GABAB receptor activation B Callaghan, A Haythornthwaite, G Berecki, RJ Clark, DJ Craik, ... Journal of Neuroscience 28 (43), 10943-10951 , 2008 2008 Citations: 205
Regulation of neuronal voltage-gated sodium channels by the ubiquitin-protein ligases Nedd4 and Nedd4-2 AB Fotia, J Ekberg, DJ Adams, DI Cook, P Poronnik, S Kumar Journal of Biological Chemistry 279 (28), 28930-28935 , 2004 2004 Citations: 200
The doublecortin-expressing population in the developing and adult brain contains multipotential precursors in addition to neuronal-lineage cells TL Walker, T Yasuda, DJ Adams, PF Bartlett Journal of Neuroscience 27 (14), 3734-3742 , 2007 2007 Citations: 195
Isolation, structure, and activity of GID, a novel α4/7-conotoxin with an extended N-terminal sequence A Nicke, ML Loughnan, EL Millard, PF Alewood, DJ Adams, NL Daly, ... Journal of Biological Chemistry 278 (5), 3137-3144 , 2003 2003 Citations: 194
The synthesis, structural characterization, and receptor specificity of the α-conotoxin Vc1. 1 RJ Clark, H Fischer, ST Nevin, DJ Adams, DJ Craik Journal of Biological Chemistry 281 (32), 23254-23263 , 2006 2006 Citations: 172
Calcium‐activated potassium channels in native endothelial cells from rabbit aorta: conductance, Ca2+ sensitivity and block. J Rusko, F Tanzi, C Van Breemen, DJ Adams The Journal of physiology 455 (1), 601-621 , 1992 1992 Citations: 165
A new level of conotoxin diversity, a non-native disulfide bond connectivity in α-conotoxin AuIB reduces structural definition but increases biological activity JL Dutton, PS Bansal, RC Hogg, DJ Adams, PF Alewood, DJ Craik Journal of Biological Chemistry 277 (50), 48849-48857 , 2002 2002 Citations: 164
