Question: Please DRAW out the mechanism and structures One challenge in the field of protein bioconjugation is the development of strategies to site-selectively modify a protein

Please DRAW out the mechanism and structures Please DRAW out the mechanism and structures One challenge in the field

One challenge in the field of protein bioconjugation is the development of strategies to site-selectively modify a protein only at a single site/residue, for example with a fluorophore. One method researchers have used is a biomimetic transamination reaction that is chemoselective for the N-terminus of proteins (ie. The reaction only modifies the N terminus of proteins). A protein (5) with a free N-terminus can react with PLP in aqueous buffer (pH=6.5) to provide a uniquely reactive Intermediate (6). Intermediate 6 can then react in a second step with an alkoxyamine substrate, such as alkoxyamine-fluorophore (7). providing a protein that is conjugated with the fluorophore through an oxime linkage (reaction scheme shown below). This reaction is considered a "biomimetic" transamination as is proceeds in the presence of PLP, but without the use of a transaminase enzyme. Provide the structure of Intermediate 6. Propose/draw a mechanism for the reaction sequence above the reaction of protein 5 and PLP to produce Intermediate 6 , and the conversion of 6 into conjugate 8 using alkoxyamine 7. Why is this reaction selective for the N-terminus amine over side-chain amines? Hint: You may want to read the attached reference (Angew. Chem. Int. Ed. 2006, 45, 5307-5311)

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