A5060475670- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Nanoparticle-Based Drug Delivery
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- RNA Interference and Gene Delivery
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Radiopharmaceutical Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Protein Degradation and Inhibitors
- Nanoplatforms for cancer theranostics
- Metal complexes synthesis and properties
- Heat shock proteins research
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Mass Spectrometry Techniques and Applications
- Cancer Treatment and Pharmacology
- Prostate Cancer Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Renin-Angiotensin System Studies
- Enzyme function and inhibition
- Prostate Cancer Treatment and Research
- Toxin Mechanisms and Immunotoxins
Washington State University
2012-2025
Cancer Targeted Technology (United States)
2025
University of Idaho
2024
University of Georgia
2017-2021
Emergence of androgen-independent cancer cells during androgen deprivation therapy presents a significant challenge to successful treatment outcomes in prostate cancer. Elucidating the role transition from an androgen-dependent state may enable development more effective therapeutic strategies against Herein, we describe vitro model for assessing effects continuous androgen-deprivation on (LNCaP) with respect expression two prostate-specific markers: receptor (AR) and membrane antigen...
Monomethyl auristatin E (MMAE) is a promising treatment option for patients diagnosed with prostate cancer (PCa); however, toxicities prevent MMAE from being administered as free drug. No MMAE-based currently marketed PCa. Herein, we describe small-molecule-drug conjugate, CTT2274, the selective delivery of MMAE. CTT2274 composed prostate-specific membrane antigen (PSMA)-binding scaffold, biphenyl motif, pH-sensitive phosphoramidate linker, and payload. We demonstrate that shows binding to...
Abstract Aberrant expression of protein arginine methyltransferases (PRMTs) has been implicated in a number cancers, making PRMTs potential therapeutic targets. But it remains not well understood how impact specific oncogenic pathways. We previously identified as important regulators cell growth neuroblastoma, deadly childhood tumor the sympathetic nervous system. Here, we demonstrate critical role for PRMT1 neuroblastoma survival. depletion decreased ability murine sphere cells to grow and...
Abstract BACKGROUND The enzyme‐biomarker prostate‐specific membrane antigen (PSMA) is an active target for imaging and therapeutic applications prostate cancer. internalization of PSMA has been shown to vary with inhibitors' mode binding: irreversible, slowly reversible, reversible. METHODS In the present study, PSMA‐targeted clickable derivatives irreversible phosphoramidate inhibitor DBCO‐PEG 4 ‐CTT‐54 (IC 50 = 1.0 nM) a reversible phosphate inhibitor, ‐CTT‐54.2 6.6 were clicked 99m Tc(CO)...
Chemical modifications of the DNA and nucleosomal histones tightly control gene transcription program in eukaryotic cells. The "histone code" hypothesis proposes that frequency, combination, location post-translational (PTMs) core compose a complex network epigenetic regulation. Currently, there are at least 23 different types >450 histone PTMs have been discovered, lysine arginine residues account for crucial part code. Although significant progress has achieved recent years, molecular...
Histone arginine methylation is a key post-translational modification that mediates epigenetic events activate or repress gene transcription. Protein methyltransferases (PRMTs) are the driving force for process of methylation, and core histone proteins have been shown to be substrates most PRMT family members. However, previous reports enzymatic activities PRMTs on histones in context nucleosomes seem contradictory. Moreover, what governs nucleosomal substrate recognition different members...
Protein homeostasis relies on the accurate translation and folding of newly synthesized proteins. Eukaryotic elongation factor 2 (eEF2) promotes GTP-dependent translocation ribosome during translation. eEF2 was recently shown to be dependent Hsp90 as well cochaperones Hgh1, Cns1, Cpr7. We examined requirement for more closely found that have two distinct roles in regulating function. Yeast expressing one group mutations or cochaperone had reduced steady-state levels eEF2. The growth mutants...
Histone arginine methylation is a prevalent posttranslational modification (PTM) in eukaryotic cells and contributes to the histone codes for epigenetic regulation of gene transcription. In this study, we determined how local changes on adjacent residues H4 substrate regulate asymmetric dimethylation symmetric catalysed by major protein methyltransferase (PRMT) enzymes PRMT1 PRMT5, respectively. We found that phosphorylation at Ser-1 site (H4S1) was inhibitory activities PRMT5 both...
Prostate cancer (PCa) is the second most common cause of death among American men after lung cancer. Unfortunately, current therapies do not provide effective treatments for patients with advanced, metastatic, or hormone refractory disease. Therefore, we seek to generate therapeutic agents a novel PCa treatment strategy by delivering suicide enzyme (yCDtriple) cell membrane bound biomarker found on cells (prostate-specific antigen (PSMA)). This approach has resulted in new reported here as...
Glutamate carboxypeptidase II (GCPII) is a membrane-bound cell surface peptidase. There significant interest in the inhibition of GCPII as means neuroprotection, while method to treat prostate cancer remains topic further investigation. The key zinc-binding functional group well-characterized classes inhibitors (phosphonates and phosphoramidates) tetrahedral negatively charged at neutral pH, glutamyl urea class possesses planar group. This study explores new inhibitors, sulfamides, which...
In this study, we present a modular synthesis and evaluation of two prostate-specific membrane antigen (PSMA) targeted small molecule drug conjugates (SMDCs) incorporating the potent chemotherapeutic agent monomethyl auristatin E (MMAE). These SMDCs are distinguished by their cleavable linker modules: one utilizing widely known valine-citrulline linker, susceptible to cleavage cathepsin B, other featuring novel acid-labile phosphoramidate-based (PhosAm) linker. Both maintained nanomolar...
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Herein, we report the modular synthesis and evaluation of a prostate-specific membrane antigen (PSMA) targeted small molecule drug conjugate (SMDC) carrying chemotherapeutic agent, SN38. Due to fluorogenic properties SN38, payload release kinetics from platform was observed in buffers representing pH conditions systemic circulation cellular internalization. It found that this is stable with minimal at physiological most rapid values endosome complex. We confirmed selective efficacy for...