Yu Ren Wang
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- Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigens1 savers
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highlights — 1427
(A) Intracellular antigens can be externalized on the cell surface or secreted, allowing targeting by antibodies. (B) Plasmids or viral vectors can be used to deliver antibody-encoding genes into the cell. Once internalized, the DNA is transcribed into the targeting antibody, which can be designed to translocate to the nucleus, mitochondria, endoplasmic reticulum (ER), or cytoplasm. (C) Nanoparticles, dendrimers, or liposomes can be used to deliver an antibody or an expression vector encoding the intracellular antibody into the target cell. (D) Antibodies can be fused to cell-penetrating pepti…
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensintracellular antibodies therapeutically represents a logical expansion of such observations
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensautoantibodies bind their intracellular target, they can cause apoptosis of the cell
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensantibodies (by processes such as endocytosis) has been observed both clinically and experimentally in the case of autoimmune disease
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigens“KDEL” or “SEKDEL” sequence
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensthus abrogating their downstream function in a similar way to RNA interference and providing an alternative strategy for silencing gene products
Frontiers | Therapeutic Antibodies against Intracellular Tumor AntigensThere are different types of intrabodies that can be tailored to target proteins within subcellular compartments, primarily the cytoplasm or the ER, but the addition of a signal peptide also allows targeting to the mitochondria or the nucleus
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensbut it is the interactions they form with other proteins or nucleic acids that are the therapeutic targets as they contribute to the diseased state.
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensantibodies within the cell can bridge the gap between small molecule inhibitors and large protein targets
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigenssmall molecules cannot physically block the large surface of such proteins, nor interfere in the protein–protein interfaces they form, which are typically hydrophobic, flat surfaces, presenting few possibilities for small molecule anchorage
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigenslarge, intracellular proteins that act as molecular scaffolds and function primarily through facilitating protein–protein interactions (PPIs).
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensleading to malignant transformation have thus far been inaccessible to small molecule inhibitors
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensdomain antibody or Dab
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigenspossible to use antibody fragments incorporating the specificity-providing regions within a single-chain variable fragment (scFv),
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensaffect protein folding and the intramolecular disulfide bonds that are required to maintain the antibody’s conformation and stability
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensthe full-length antibody is not functional in the cytosol, prior to secretion, due to its reducing conditions
Frontiers | Therapeutic Antibodies against Intracellular Tumor AntigensThey are synthesized in the endoplasmic reticulum (ER) of B cells as separate heavy chain and light chains
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensantibodies that are produced in the cell, and bind an antigen within the same cell
Frontiers | Therapeutic Antibodies against Intracellular Tumor AntigensIntracellular antibodies, which may also be called intrabodies
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensheat-shock proteins 70 and 90 are chaperone proteins, which are further examples of targets that are intracellular in normal cells but become presented on the cell surface, or secreted into the extracellular environment, in transformed cells
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensmelanosome, a specialized organelle present in melanocytes
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensintracellular melanosomal membrane glycoprotein, gp75
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensundetectable in most normal human tissues, is involved in colorectal cancer and uveal melanoma, and is overexpressed in 85% of gastric cancers
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensphosphatase of regenerating liver 3 (PRL-3) and developed a humanized anti-PRL-3 antibody
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensdichotomy between the antibody targeting of intracellular and extracellular targets is not as rigid as originally thought
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigens(3) Antibodies can also be generated that bind cell surface major histocompatibility complex class I (MHC-I)-presented peptides that are derived from intracellular proteins.
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigens(2) It is also possible to engineer antibodies or antibody fragments that penetrate into cells, or those that are directly expressed within cells using a gene therapy style approach.
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigens(1) It is possible for antibodies (or their derivatives) to target antigens that are normally intracellular but become externalized (for example, during disease).
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigensantibodies, small molecules tend not to be as selective for their targets
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigenssmall molecules have been used to target those intracellular antigens with a functionality that is suitable for drug screening
Frontiers | Therapeutic Antibodies against Intracellular Tumor AntigensHistorically the consensus in the immunotherapy field has been that antibody therapy is amenable to targeting only extracellular antigens that are accessible for antibody binding. This is due to the fact that the high molecular weight of antibodies prevents them from crossing the cell membrane to access intracellular targets
Frontiers | Therapeutic Antibodies against Intracellular Tumor AntigensThese tumor-associated peptide–MHC-I complexes can then be targeted by antibodies known as T-cell receptor mimic (TCRm) or T-cell receptor (TCR)-like antibodies
Frontiers | Therapeutic Antibodies against Intracellular Tumor AntigensAdvances in the production of TCRm antibodies have enabled the generation of multiple TCRm antibodies
Frontiers | Therapeutic Antibodies against Intracellular Tumor Antigens'pre-fabricated' in the form of orotate
10.5: N-glycosidic Bonds - Chemistry LibreTextspyrimidine ribonucleotides and (U, C and T) also begins with PRPP
10.5: N-glycosidic Bonds - Chemistry LibreTextsphosphoribosylpyrophosphate (PRPP)
10.5: N-glycosidic Bonds - Chemistry LibreTextspurine (G and A) ribonucleotides
10.5: N-glycosidic Bonds - Chemistry LibreTextsrest of the purine base is assembled piece by piece by other biosynthetic enzymes
10.5: N-glycosidic Bonds - Chemistry LibreTextsThe inorganic pyrophosphate then leaves to generate a resonance-stabilized carbocation
10.5: N-glycosidic Bonds - Chemistry LibreTextsfive-carbon sugar called ribose-5-phosphate
10.5: N-glycosidic Bonds - Chemistry LibreTextsN-glycosidic bond. You may recognize these as the bonds in nucleosides and nucleotides that link the G, C, A, T, or U base to the sugar.
10.5: N-glycosidic Bonds - Chemistry LibreTextscatalyze the cleavage of glycosidic bonds in carbohydrates
10.4: Acetals and Ketals - Chemistry LibreTextsapplies to reactions catalyzed by glycosidase enzymes
10.4: Acetals and Ketals - Chemistry LibreTextsIn step 1, an alcohol is protonated by a nearby acid group as it breaks away to form a resonance-stabilized carbocation intermediate. The carbocation is attacked by a nucleophilic water molecule in step 2 to form a hemiacetal
10.4: Acetals and Ketals - Chemistry LibreTextsThe UDP group on glucose-UDP then leaves (step 1 below), forming a resonance-stabilized carbocation intermediate
10.4: Acetals and Ketals - Chemistry LibreTextsfirst activated through two enzymatic phosphate transfer steps
10.4: Acetals and Ketals - Chemistry LibreTextsorganic chemistry terms these reactions represent the conversion of a hemiacetal to an acetal (remember that sugar monomers in their cyclic form are hemiacetals and hemiketals).
10.4: Acetals and Ketals - Chemistry LibreTextsconversion of a hemiacetal to an acetal
10.4: Acetals and Ketals - Chemistry LibreTextsReactions in which new glycosidic bonds are formed are catalyzed by enzymes called glycosyltransferases
10.4: Acetals and Ketals - Chemistry LibreTextsthat carbon #1, the anomeric carbon on the left-side glucose monomer, is the central carbon of an acetal group
10.4: Acetals and Ketals - Chemistry LibreTexts