title: Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy.
abstract: Signal transduction pathways, which control the response of cells to various environmental signals, are mediated by the function of signaling proteins that interact with each other and activate one other with high specificity. Synthetic agents that mimic the function of these proteins might therefore be used to generate unnatural signal transduction steps and consequently, alter the cell's function. We present guidelines for designing 'chemical transducers' that can induce artificial communication between native proteins. In addition, we present detailed protocols for synthesizing and testing a specific 'transducer', which can induce communication between two unrelated proteins: platelet-derived growth-factor (PDGF) and glutathione-S-transferase (GST). The way by which this unnatural PDGF-GST communication could be used to control the cleavage of an anticancer prodrug is also presented, indicating the potential for using such systems in 'artificial signal transduction therapy'. This work is intended to facilitate developing additional 'transducers' of this class, which may be used to mediate intracellular protein-protein communication and consequently, to induce artificial cell signaling pathways.
authors: Department of Organic Chemistry, Weizmann Institute of Science.
authors: Ronny
authors: R
authors: Peri-Naor
authors: Department of Organic Chemistry, Weizmann Institute of Science.
authors: Leila
authors: L
authors: Motiei
authors: Department of Organic Chemistry, Weizmann Institute of Science; david.margulies@weizmann.ac.il.
authors: David
authors: D
authors: Margulies
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism*; D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000494:pharmacology*; D001391:Azo Compounds / Q000378:metabolism*; D002468:Cell Physiological Phenomena; D060326:Chemistry Techniques, Synthetic; D005982:Glutathione Transferase / Q000737:chemistry / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010879:Piperazines / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D001391:Azo Compounds; C474958:O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011355:Prodrugs; D009569:Nitric Oxide; D005982:Glutathione Transferase