01-ERD-111 - The Development of Synthetic High Affinity Ligands

Perkins, J ; Balhorn, R ; Cosman, M ; Lightstone, F ; Zeller, L

Lawrence Livermore National Laboratory

关键词: National Security;    37 Inorganic, Organic, Physical And Analytical Chemistry;    59 Basic Biological Sciences;    Radiotherapy;    Ligands;   

DOI  :  10.2172/15013987
RP-ID  :  UCRL-TR-202374
RP-ID  :  W-7405-ENG-48
RP-ID  :  15013987

美国|英语

来源: UNT Digital Library

【 摘 要 】

The aim of this project was to develop Synthetic High-Affinity Ligands (SHALs), which bind with high affinity and specificity to proteins of interest for national security and cancer therapy applications. The aim of producing synthetic ligands for sensory devices as an alternative to antibody-based detection assays and therapeutic agents is to overcome the drawbacks associated with antibody-based in next-generation sensors and systems. The focus area of the project was the chemical synthesis of the SHALs. The project concentrated on two different protein targets. (a) The C fragment of tetanus and botulinum toxin, potential biowarfare agents. A SHAL for tetanus or botulinum toxin would be incorporated into a sensory device for the toxins. (b) HLA-DR10, a protein found in high abundance on the surface of Non-Hodgkins Lymphoma. A SHAL specific to a tumor marker, labeled with a radionuclide, would enable the targeted delivery of radiation therapy to metastatic disease. The technical approach used to develop a SHAL for each protein target will be described in more detail below. However, in general, the development of a SHAL requires a combination of computational modeling techniques, modern nuclear magnetic resonance spectroscopy (NMR) and synthetic chemistry.