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To apply this methodology to the anti-Met macrocycles, we designed precursor macrocycles bearing a short peptide motif containing a Cys residue at the C terminus and modified the sulfhydryl group with three bis-maleimide cross-linkers with different lengths, C6, PEG3 and PEG11 (Supplementary Table 2)

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High heat rapidly accelerates the degradation of delicate peptide bonds through hydrolysis and deamidation, a process that can render a highly pure research compound entirely useless before it ever reaches the laboratory bench