Non-Immunoglobulin Synthetic Binding Proteins for Oncology
David T.I. Pestov N.B. Korneenko T.V. Barlev N.A.
September 2023
Biochemistry (Moscow)
2023#88Issue 91232 - 1247 pp.
Abstract: Extensive application of technologies like phage display in screening peptide and protein combinatorial libraries has not only facilitated creation of new recombinant antibodies but has also significantly enriched repertoire of the protein binders that have polypeptide scaffolds without homology to immunoglobulins. These innovative synthetic binding protein (SBP) platforms have grown in number and now encompass monobodies/adnectins, DARPins, lipocalins/anticalins, and a variety of miniproteins such as affibodies and knottins, among others. They serve as versatile modules for developing complex affinity tools that hold promise in both diagnostic and therapeutic settings. An optimal scaffold typically has low molecular weight, minimal immunogenicity, and demonstrates resistance against various challenging conditions, including proteolysis – making it potentially suitable for peroral administration. Retaining functionality under reducing intracellular milieu is also advantageous. However, paramount to its functionality is the scaffold’s ability to tolerate mutations across numerous positions, allowing for the formation of a sufficiently large target binding region. This is achieved through the library construction, screening, and subsequent expression in an appropriate system. Scaffolds that exhibit high thermodynamic stability are especially coveted by the developers of new SBPs. These are steadily making their way into clinical settings, notably as antagonists of oncoproteins in signaling pathways. This review surveys the diverse landscape of SBPs, placing particular emphasis on the inhibitors targeting the oncoprotein KRAS, and highlights groundbreaking opportunities for SBPs in oncology.
adnectins , affibodies , DARPins , lipocalins , monobodies
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Institute of Biomedical Chemistry, Moscow, 119121, Russian Federation
Laboratory of Molecular Oncology, Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Moscow Region, Dolgoprudny, 141701, Russian Federation
Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides, Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences, Moscow, 108819, Russian Federation
Group of Cross-Linking Enzymes, Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russian Federation
Institute of Cytology Russian Academy of Sciences, St.-Petersburg, 194064, Russian Federation
School of Medicine, Nazarbayev University, Astana, 010000, Kazakhstan
Institute of Biomedical Chemistry
Laboratory of Molecular Oncology
Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitides
Group of Cross-Linking Enzymes
Institute of Cytology Russian Academy of Sciences
School of Medicine
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