Brief description not available

Brief description not available

Researchers at the University of California, Davis have developed novel serotonin receptor modulators designed as mixed 5-HT2A/2C partial agonists that demonstrate promising disease-modifying potential for Parkinson’s Disease with improved safety and efficacy.

Researchers at the University of California, Davis have developed a novel class of compounds for modulating serotonin receptors, offering potential treatment for various psychiatric and neurological disorders without inducing hallucinogenic effects.

Combinatorial encoded library technologies can provide a set of tools for discovering protein-targeting ligands (molecules) and for drug discovery. These techniques can accelerate ligand discovery by leveraging chemical diversity achievable through genetically encoded combinatorial libraries, for example, by combinatorial permutation of chemical building blocks. Although display technologies such as mRNA and phage display use biological translation machinery to produce peptide-based libraries, hits from these libraries often lack key drug-like properties, for example, cell permeability. This limitation can arise from the peptide backbone's inherent polarity and the tendency to select compounds with polar/charged side chains. Backbone N-methylation can increase scaffold lipophilicity in mRNA display; however, codon table constraints can necessitate longer sequences to fully utilize the available space.DNA-encoded libraries (DELs) offer an alternative approach towards discovering hits against drug targets. However, like other encoded library techniques, DELs face significant obstacles in affinity selections, which tend to enrich library members bearing polar and/or charged moieties, which can have low (poor) passive cell membrane permeability, especially in larger molecular weight libraries, resulting in hits with poor drug-like properties. This selection bias is especially problematic for larger constructs beyond the rule of 5, where fine-tuning lipophilicity can be critical. Furthermore, DNA-encoded libraries can be of low quality. Although algorithmic predictions of lipophilicity exist, these two-dimensional (2D) atomistic calculations cannot capture conformational effects exhibited by larger molecules like peptide macrocycles. Despite over a decade of DEL technology development, no method exists to measure physical properties of encoded molecules across an entire DNA-encoded library. That is, successful translation of hits from encoded library selections can be impeded by low quality libraries and enrichment of highly polar members which tend to have poor passive cell permeability, especially for larger molecular weight libraries.DELs are produced through split-pool synthesis with DNA barcoding to encode the building block of each chemical step. Although this approach can draw on a large number of building blocks and allow for the formation of non-peptidic libraries with a large number of members, synthetic challenges persist. The formation of DELs can be synthetically inefficient. Truncations multiply ( are compounded) throughout synthesis, reducing the representation of properly synthesized constructs. Although strategies to improve library purity, to enable reaction monitoring for macrocycle formation, and to identify problematic chemistry affecting DNA tag amplification may be applied, a direct method for assessing DEL quality on a library-wide basis has yet to be developed.   

Antibiotic resistance is a major issue in infectious disease treatment and prevention. In bacteria, the type III secretion system (T3SS) secretes effector proteins in the host cell, allowing the pathogen to infect. The T3SS is largely found on pathogens and not beneficial bacteria, so targeting the T3SS might have an advantage over using classic antibiotics, which disturb the beneficial human microbiome.

Researchers at the University of California, Davis have developed a therapeutic use of cannabinoids for the treatment of Neurodegenerative Disorders (NDDs).

A revolutionary approach to treating stone disease and improving ureteral distensibility through pharmacological means.

A revolutionary drug modality for the selective modification and degradation of intracellular proteins in lysosomes.

Stability issues in membrane-free coacervates have been addressed with coating strategies, but these approaches often compromise the permeability of the coacervate. Researchers from UC San Diego have invented a facile approach to maintain both stability and permeability using tannic acid and then demonstrate the value of this approach in enzyme-triggered drug release. First, the researchers developed size-tunable coacervates via self-assembly of heparin glycosaminoglycan with tyrosine and arginine-based peptides. A thrombin-recognition site within the peptide building block results in heparin release upon thrombin proteolysis. Notably, polyphenols are integrated within the nano-coacervates to improve stability in biofluids. Phenolic crosslinking at the liquid-liquid interface enables nano-coacervates to maintain exceptional structural integrity across various environments. The UCSD scientists discovered a pivotal polyphenol threshold for preserving enzymatic activity alongside enhanced stability. The disassembly rate of the nano-coacervates increases as a function of thrombin activity, thus preventing a coagulation cascade. This polyphenol-based approach not only improves stability but also opens the way for applications in biomedicine, protease sensing, and bio-responsive drug delivery. 

An innovative mid-throughput technique for screening and optimizing threose nucleic acid (TNA) aptamers for protein-binding activity.

The challenge in utilizing α-Linolenic acid (ALA) for medical adhesives has been its poor water solubility and the high hydrophobicity of poly(ALA), typically necessitating elevated temperatures, organic solvents, or complex preparation methods for tissue application. UC Berkeley researchers have developed ALA-based powder and low-viscosity liquid superglues that overcome this limitation by polymerizing and bonding rapidly upon contact with wet tissue. The versatile adhesives are formulated using a monomeric mixture of ALA, sodium lipoate, and an activated ester of lipoic acid. These adhesives demonstrate high flexibility, cell and tissue compatibility, biodegradability, and potential for sustained drug delivery as a small molecule regenerative drug was successfully incorporated and released without altering the adhesive's properties. Additionally, the inherent ionic nature of the adhesives provides high electric conductivity and sensitivity to deformation, enabling their use as a tissue-adherent strain sensor.

Endosomal sorting complexes required for transport (ESCRT) pathways are integral to critical cellular processes, and their dysfunction is associated with neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. This innovation from UC Berkeley researchers provides compounds that activate VPS4B, VPS4A, or both, which are key components of these ESCRT pathways. These activators offer a novel approach to addressing diseases linked to endosomal-lysosomal and autophagic dysfunction. In comparison to alternatives, these compounds are unique in their ability to activate the VPS4 ATPases.

Dysfunction in endosomal-lysosomal and autophagic activity is a critical factor in neurodegenerative disorders like Parkinson’s and Alzheimer’s Disease. This innovation, developed by UC Berkeley researchers, addresses this by providing compounds that act as activators of the AAA+ ATPases VPS4B, VPS4A, or both, which are key components of the ESCRT (Endosomal sorting complexes required for transport) pathways. The compounds are useful for both therapeutic intervention in these diseases and as essential research reagents, offering a unique mechanism to study the effect of ESCRT pathways in biological systems.

The oncogenic transcription factor MYC is implicated in a vast number of human cancers, yet it has proven exceptionally difficult to target using conventional small-molecule inhibitors due to its intrinsically disordered nature. This innovation, developed by UC Berkeley researchers, addresses the urgent need for a novel therapeutic strategy by introducing a class of compounds and pharmaceutical compositions that achieve the stereoselective covalent destabilizing degradation of the MYC protein.

Researchers at the University of California, Davis have developed an algorithm for designing and identifying complex structures having custom release profiles for controlled drug delivery.

This invention describes a novel method for the inhibition of specific potassium ion channels, particularly TWIK-related arachidonic acid-activated K+ channels (TRAAK), using cannabinoid compounds. The research demonstrates that these compounds can be used to modulate the function of these channels, which are implicated in various neurological and physiological disorders, including epilepsy. This approach presents a new pharmacological strategy for targeting these channels and developing treatments for associated conditions.

This innovation addresses the limitations of producing proteins with non-natural monomers (NNMs), which have valuable applications in drug discovery and materials science. Researchers at UC Berkeley have developed novel PylRS-tRNAPyl pairs that enable the efficient incorporation of NNMs into proteins. This technology provides a significant advantage over existing methods by offering a broader range of NNM incorporation with high specificity and efficiency.Provided are compositions and methods for creating proteins that contain non-natural monomers (NNMs) using new PylRS-tRNAPyl pairs.  This technology works by introducing a subject PylRS, a tRNA, and an NNM into a host system, such as a bacterial cell, eukaryotic cell, or an in vitro translation system, allowing the tRNA to be acylated with the NNM by the PylRS.

Researchers at the University of California, Davis have developed advanced compounds targeting neuraminidase activity to combat viral infections and understand cellular mechanisms.

Researchers at the University of California, Davis, have developed new synthesis methods for the rapid and highly pure production of glycosphingolipids. The prototyped process can produce pure glycosphingolipids that can be used within basic disease research and drug and diagnostic development.

         While nuclear magnetic resonance (NMR) is one of the most universal synthetic chemistry tools for its ability to measure highly specific kinetic and structural information nondestructively/noninvasively, it is costly and low-throughput primarily due to the small sample-size volumes and expensive equipment needed for stringent magnetic field homogeneity. Conversely, zero-to-ultralow field (ZULF) NMR is an emerging alternative offering similar chemical information but relaxing field homogeneity requirements during detection. ZULF NMR has been further propelled by recent advancements in key componentry, optically pumped magnetometers (OPMs), but suffers in scope due to its low sensitivity and its susceptibility to noise. It has not been possible to detect most organic molecules without resorting to hyperpolarization or 13C enrichment using ZULF NMR.         To overcome these challenges, UC Berkeley researchers have developed a multi-channel ZULF spectrometer that greatly improves on both the sensitivity and throughput abilities of state-of-the art ZULF NMR devices. The novel spectrometer was used in the first reported detection of organic molecules in natural isotopic abundance by ZULF NMR, with sensitivity comparable to current commercial benchtop NMR spectrometers. A proof-of-concept multichannel version of the ZULF spectrometer was capable of measuring three distinct chemical samples simultaneously. The combined sensitivity and throughput distinguish the present ZULF NMR spectrometer as a novel chemical analysis tool at unprecedented scales, potentially enabling emerging fields such as robotic chemistry, as well as meeting the demands of existing fields such as chemical manufacturing, agriculture, and pharmaceutical industries.

         Recent advancements in nuclear magnetic resonance (NMR) spectroscopy have underscored the need for novel instrumentation, but current commercial instrumentation performs well primarily for pre-existing, mainstream applications. Modalities involving, in particular, integrated electron-nuclear spin control, dynamic nuclear polarization (DNP), and non-traditional NMR pulse sequences would benefit greatly from more flexible and capable hardware and software. Advances in these areas would allow many innovative NMR methodologies to reach the market in the coming years.          To address this opportunity, UC Berkeley researchers have developed a novel high-speed, high-memory NMR spectrometer and hyperpolarizer. The device is compact, rack-mountable and cost-effective compared to existing spectrometers. Furthermore, the spectrometer features robust, high-speed NMR transmit and receive functions, synthesizing and receiving signals at the Larmor frequency and up to 2.7GHz. The spectrometer features on-board, phase-sensitive detection and windowed acquisition that can be carried out over extended periods and across millions of pulses. These and additional features are tailored for integrated electron-nuclear spin control and DNP. The invented spectrometer/hyperpolarizer opens up new avenues for NMR pulse control and DNP, including closed-loop feedback control, electron decoupling, 3D spin tracking, and potential applications in quantum sensing.

Researchers at the University of California, Davis have developed improved variants of a Heparosan synthase supporting efficient synthesis of heparosan, heparin, and heparan sulfate analogs.

Lipoxygenases (LOX) are enzymes that catalyze the peroxidation of certain fatty acids. The cell membrane is mostly made of lipids (which include fatty acids), and peroxidation can cause damage to the cell membrane. The human genome contains six functional LOX genes that encode for six LOX enzyme variants, or isozymes. The role that each LOX isozyme plays in health and disease varies greatly, spanning issues such as asthma, diabetes, and stroke. LOX enzymes are extremely difficult to target due to high hydrophobicity. Potential leads are often ineffective because they are either not readily soluble or not selective for a particular LOX enzyme.  Studies have implicated human epithelial 15-lipoxygenase-2 (h15-LOX-2, ALOX15B) in various diseases. h15-LOX-2 is highly expressed in atherosclerotic plaques and is linked to the progression of macrophages to foam cells, which are present in atherosclerotic plaques. h15-LOX-2 mRNA levels are also highly elevated in human macrophages isolated from carotid atherosclerotic lesions in symptomatic patients. Children with cystic fibrosis had reduced levels of h15-LOX-2, which affects the lipoxin A4 to leukotriene B4 ratio. Furthermore, the interactions of h15-LOX-2 and PEBP1 changes the substrate specificity of h15-LOX-2 from free polyunsaturated fatty acids (PUFA) to PUFA-phosphatidylethanolamines (PE), leading to the generation of hydroperoxyeicosatetraenoic acid (HpETE) esterified into PE (HpETE-PE). Accumulation of these hydroperoxyl membrane phospholipids has been shown to cause ferroptotic cell death, which implicates h15-LOX-2 in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.  

Researchers at the University of California, Davis have developed a virally derived homolog to increase the inflammatory response desirable in cancer immunotherapy.