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Historical Background and Scientific Context Scientific interest in peptide fragments expanded significantly as researchers sought to better understand structure-function relationships within naturally occurring peptide hormones

incorporated hypoxia-labile groups e.g., (1-methyl-2-nitro-1H-imidazol-5-yl)methyl or 4-nitrobenzyl into an EGFRdel19-targeting PROTAC, yielding ha-PROTACs 17 and 18 (Fig