[
    {
        "id": "thesis:17616",
        "collection": "thesis",
        "collection_id": "17616",
        "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:08122025-011509478",
        "primary_object_url": {
            "basename": "Samkian_2026 Thesis.pdf",
            "content": "final",
            "filesize": 50130987,
            "license": "other",
            "mime_type": "application/pdf",
            "url": "/17616/4/Samkian_2026 Thesis.pdf",
            "version": "v5.0.0"
        },
        "type": "thesis",
        "title": "Total Synthesis of Hypersampsone M and Studies of Related Polycyclic Polyprenylated Acylphloroglucinol Systems",
        "author": [
            {
                "family_name": "Samkian",
                "given_name": "Adrian Eduard",
                "orcid": "0000-0002-0068-3572",
                "clpid": "Samkian-Adrian-Eduard"
            }
        ],
        "thesis_advisor": [
            {
                "family_name": "Stoltz",
                "given_name": "Brian M.",
                "orcid": "0000-0001-9837-1528",
                "clpid": "Stoltz-B-M"
            }
        ],
        "thesis_committee": [
            {
                "family_name": "Fu",
                "given_name": "Gregory C.",
                "orcid": "0000-0002-0927-680X",
                "clpid": "Fu-G-C"
            },
            {
                "family_name": "Reisman",
                "given_name": "Sarah E.",
                "orcid": "0000-0001-8244-9300",
                "clpid": "Reisman-S-E"
            },
            {
                "family_name": "Goddard",
                "given_name": "William A., III",
                "orcid": "0000-0003-0097-5716",
                "clpid": "Goddard-W-A-III"
            },
            {
                "family_name": "Virgil",
                "given_name": "Scott C.",
                "orcid": "0000-0001-8586-5641",
                "clpid": "Virgil-S-C"
            },
            {
                "family_name": "Stoltz",
                "given_name": "Brian M.",
                "orcid": "0000-0001-9837-1528",
                "clpid": "Stoltz-B-M"
            }
        ],
        "local_group": [
            {
                "literal": "div_chem"
            }
        ],
        "abstract": "Research in the Stoltz group is primarily focused on the total synthesis of complex, bioactive natural products and on the development of reaction methodologies to enable these synthetic endeavors. This thesis focuses on the homoadamantane polycyclic polyprenylated acylphloroglucinol (PPAP) class of natural products, our efforts toward their synthesis, and discoveries made along the way. Chapter 1 describes the completed synthesis of hypersampsone M, while Chapter 2 describes ongoing efforts toward wilsonglucinol G and hypersampsone A. Appendix 5 presents the culmination of optimization studies and unsuccessful routes toward these natural products. Chapter 3 describes selective fragmentations of a-bromocaranones, reactions that were tailored to the synthesis of PPAPs. Chapter 4 discloses the synthesis and characterization of an unexpected, caged side product isolated during an unsuccessful route to the homoadamantane PPAPs. Chapter 5 discusses the development and scope of the key cyclopentene annulation methodology that enabled the installation of the challenging, hindered 5-membered ring on the homoadamantane PPAPs.",
        "doi": "10.7907/hd4h-sk15",
        "publication_date": "2026",
        "thesis_type": "phd",
        "thesis_year": "2026"
    },
    {
        "id": "thesis:17303",
        "collection": "thesis",
        "collection_id": "17303",
        "cite_using_url": "https://resolver.caltech.edu/CaltechTHESIS:05302025-004839918",
        "primary_object_url": {
            "basename": "Thesis_Maryann_Morales.pdf",
            "content": "final",
            "filesize": 5588826,
            "license": "other",
            "mime_type": "application/pdf",
            "url": "/17303/2/Thesis_Maryann_Morales.pdf",
            "version": "v6.0.0"
        },
        "type": "thesis",
        "title": "Metal Binding to Nsp1, a SARS-CoV-2 Protein",
        "author": [
            {
                "family_name": "Morales",
                "given_name": "Maryann",
                "orcid": "0000-0002-1778-8901",
                "clpid": "Morales-Maryann"
            }
        ],
        "thesis_advisor": [
            {
                "family_name": "Gray",
                "given_name": "Harry B.",
                "orcid": "0000-0002-7937-7876",
                "clpid": "Gray-H-B"
            }
        ],
        "thesis_committee": [
            {
                "family_name": "Hadt",
                "given_name": "Ryan G.",
                "orcid": "0000-0001-6026-1358",
                "clpid": "Hadt-Ryan-G"
            },
            {
                "family_name": "Winkler",
                "given_name": "Jay Richmond",
                "orcid": "0000-0002-4453-9716",
                "clpid": "Winkler-J-R"
            },
            {
                "family_name": "Okumura",
                "given_name": "Mitchio",
                "orcid": "0000-0001-6874-1137",
                "clpid": "Okumura-M"
            },
            {
                "family_name": "Rees",
                "given_name": "Douglas C.",
                "orcid": "0000-0003-4073-1185",
                "clpid": "Rees-D-C"
            },
            {
                "family_name": "Virgil",
                "given_name": "Scott C.",
                "orcid": "0000-0001-8586-5641",
                "clpid": "Virgil-S-C"
            },
            {
                "family_name": "Gray",
                "given_name": "Harry B.",
                "orcid": "0000-0002-7937-7876",
                "clpid": "Gray-H-B"
            }
        ],
        "local_group": [
            {
                "literal": "div_chem"
            }
        ],
        "abstract": "<p>The COVID-19 pandemic, caused by SARS-CoV-2, has underscored the need for novel antiviral strategies beyond vaccines. A key virulence factor in SARS-CoV-2 is nonstructural protein 1 (Nsp1), which suppresses host immune responses by degrading mRNA, inhibiting nuclear export, and binding to the 40S ribosomal subunit to block host translation. Its intrinsically disordered C-terminal domain complicates structure-based drug design, prompting exploration of alternative approaches.</p>\r\n\r\n<p>This work investigates the use of transition metal coordination to target disordered regions of Nsp1. Copper(II) and cobalt(III) complexes were examined for their ability to bind histidine residues\u2014particularly H165, critical for ribosome interaction. Biophysical techniques, including fluorescence spectroscopy, EPR, and \u2075\u2079Co NMR, along with computational modeling, were used to characterize binding to Nsp1-derived peptides and the full-length protein.</p>\r\n\r\n<p>Cu(II) displayed pH-dependent coordination through histidine and backbone amides, while oxidized Co(III) complexes formed stable, substitution-inert interactions. Multi-site binding and distinct kinetic profiles were observed. In vitro translation assays showed that metal complexes can affect translation, though selective inhibition of Nsp1 remains challenging.Overall, this work provides a foundation for targeting disordered viral proteins using coordination chemistry.</p>",
        "doi": "10.7907/z9m9-yn02",
        "publication_date": "2025",
        "thesis_type": "phd",
        "thesis_year": "2025"
    }
]