Synthesis of Vascular Disrupting Agent Payloads, Protease Specific Linkers, and their Corresponding Constructs

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dc.contributor.advisorPinney, Kevin G.
dc.contributor.authorSmith, Abigail B.
dc.contributor.departmentUniversity Scholar.en_US
dc.contributor.otherJacob W. Forden_US
dc.contributor.otherBaylor Universityen_US
dc.contributor.schoolshonors collegeen_US
dc.date.accessioned2020-05-20T12:45:09Z
dc.date.available2020-05-20T12:45:09Z
dc.date.copyright2020
dc.date.issued2020-05-20
dc.description.abstractThe discovery and development of small-molecule anticancer agents that are both highly efficacious and selectively targeted remains a formidable goal and challenge. Conventional chemotherapy regimens often employ the use of cytotoxic agents which fail to differentiate between normal and cancerous tissue and are thus limited by their high degree of toxicity to normal tissue. Antibody-drug conjugates (ADCs) represent an emerging class of biopharmaceutical therapeutics that deliver highly potent anticancer agents (payloads) selectively to tumors or components of the tumor microenvironment. ADCs are comprised of a drug (payload) which is joined through an appropriate linker to an antibody or engineered protein. Pairing both a high degree of selectivity through the antibody with a high degree of cytotoxicity through the payload, ADCs represent an emerging and promising class of chemotherapeutic agents. Two small-molecule payloads (KGP05 and KGP18, previously discovered in the Pinney Laboratory) function as both highly potent antiproliferative agents (cytotoxins) and as highly effective vascular disrupting agents (VDAs). Details regarding the synthesis of these payloads and the preparation of drug-linker constructs tethering these payloads to the protease cleavable dipeptide linker Val-Cit-PABOH, widely used in ADC research, are presented.en_US
dc.identifier.urihttps://hdl.handle.net/2104/10866
dc.language.isoen_USen_US
dc.rightsBaylor University projects are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission.en_US
dc.rights.accessrightsWorldwide accessen_US
dc.rights.accessrightsAccess changed 8/24/22
dc.subjectSynthetic organic chemistry.en_US
dc.subjectMedicinal chemistry.en_US
dc.subjectVascular disrupting agents (VDAs).en_US
dc.subjectAntibody drug conjugates (ADCs).en_US
dc.titleSynthesis of Vascular Disrupting Agent Payloads, Protease Specific Linkers, and their Corresponding Constructsen_US
dc.typeThesisen_US

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