A5022346131- Estrogen and related hormone effects
- Synthesis and biological activity
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Free Radicals and Antioxidants
- Click Chemistry and Applications
- Prostate Cancer Treatment and Research
- Radiopharmaceutical Chemistry and Applications
- Synthesis and Characterization of Heterocyclic Compounds
- Ferrocene Chemistry and Applications
- Metal complexes synthesis and properties
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Crystal structures of chemical compounds
- Medical Imaging Techniques and Applications
- HER2/EGFR in Cancer Research
- Mass Spectrometry Techniques and Applications
- Protein Degradation and Inhibitors
- Organic Chemistry Cycloaddition Reactions
- Analytical Chemistry and Chromatography
- Cancer, Stress, Anesthesia, and Immune Response
- Regulation of Appetite and Obesity
Virginia Tech
2016-2018
University of Arizona
2007-2015
University of Illinois Urbana-Champaign
2013
Translational Genomics Research Institute
2009
National Institute of Pharmaceutical Education and Research
2006
A challenge in tumor targeting is to deliver payloads cancers while sparing normal tissues. limited number of antibodies appear meet this as therapeutics themselves or drug-antibody conjugates. However, suffer from their large size, which can lead unfavorable pharmacokinetics for some therapeutic payloads, and that they are targeted against only a single epitope, reduce selectivity specificity. Here, we propose an alternative approach based on patterns cell surface proteins rationally...
Abstract Some estrogen receptor‐α ( ER α)‐targeted breast cancer therapies such as tamoxifen have tissue‐selective or cell‐specific activities, while others similar activities in different cell types. To identify biophysical determinants of signaling and proliferation, we synthesized 241 α ligands based on 19 chemical scaffolds, compared ligand response using quantitative bioassays for canonical X‐ray crystallography. Ligands that regulate the dynamics stability coactivator‐binding site...
Together we bind: A series of synthetic heterobivalent ligands containing a fragment melanocyte stimulating hormone analogue MSH(7) and the δ-opioid ligand deltorphin-II has been prepared. These bind with higher affinity apparent cooperativity to cells expressing both hMC4R receptors. Binding affinities were evaluated using lanthanide-based in-cyto time-resolved fluorescence binding assay. Supporting information for this article is available on WWW under...
Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept functionally unrelated can be noncovalently cross-linked with high avidity and specificity, series heterobivalent (htBVLs) were...
We demonstrate the potential utility of multivalent ligands as targeting agents for cancer imaging or therapy by determining binding homobivalent to their corresponding receptors. This manuscript details synthesis and evaluation a series bivalent containing two copies truncated heptapeptide version [Nle4-d-Phe7]-α-melanocyte stimulating hormone (NDP-α-MSH), referred MSH(7). These were connected with various semirigid linkers Pro-Gly repeats, without flexible poly(ethylene glycol) (PEGO)...
Abstract A novel approach to specifically target tumor cells for detection and treatment is the proposed use of heteromultivalent ligands, which are designed interact with, noncovalently crosslink, multiple different cell surface receptors. Although enhanced binding has been shown synthetic homomultivalent proof cross-linking requires ligands with two or more moieties. As proof-of-concept, we have examined heterobivalent lines that were engineered coexpress G-protein-coupled human receptors,...
The incidence of malignant melanoma is rising faster than that any other cancer in the United States. Because its high expression on surface melanomas, MC1R has been investigated as a target for selective imaging and therapeutic agents against melanoma. Eight ligands were screened cell lines engineered to overexpress MC1R, MC4R, or MC5R. Of these, compound 1 (4-phenylbutyryl-His-dPhe-Arg-Trp-NH(2)) exhibited (0.2 nM) binding affinity low (high nanomolar) affinities MC4R Functionalization...
A general solid-phase synthetic strategy is developed to prepare fluorescent and/or lanthanide-labeled derivatives of the δ-opioid receptor (δOR) ligand H-Dmt-Tic-Lys(R)-OH. The high δ-OR affinity (Ki = 3 nM) and desirable in vivo characteristics Cy5 derivative 1 suggest its usefulness for structure−function studies localization as a high-contrast noninvasive molecular marker live imaging ex or vivo.
Fluorescence molecular imaging can be employed for the development of novel cancer targeting agents. Herein, we investigated pharmacokinetics (PK) and cellular uptake Dmt-Tic-Cy5, a delta-opioid receptor (δOR) antagonist-fluorescent dye conjugate, as tumor-targeting agent. δOR expression is observed normally in CNS, pathologically some tumors, including lung liver breast cancers. In vitro, vivo, ex vivo experiments were conducted to image quantify fluorescence signal associated with...
Gemeinsame Anbindung: Eine Reihe synthetischer heterodivalenter Liganden aus einem Fragment des melanozytenstimulierenden Hormonanalogons MSH(7) und dem δ-Opioidligand Deltorphin-II wurde synthetisiert. Diese binden mit gesteigerter Affinität offenbar kooperativ an Zellen, die sowohl hMC4R als auch δ-Opioidrezeptoren exprimieren. Die Bindungsaffinitäten wurden in den Zellen zeitauflösenden Lanthanoidfluoreszenz-Bindungsassay bestimmt. Supporting information for this article is available on...
Abstract Current treatments for prostate cancer are centered on blocking androgen-signaling axis, which is the target of several clinical androgen receptor (AR) antagonists such as enzalutamide. Recent studies have shown that a single AR mutation (F876L) converts enzalutamide from an antagonist to agonist—a fate shared by earlier well bicalutamide and flutamide. While hormonal therapy often successful in initial stages disease, prostatic tumors inevitably become resistant these therapeutics....