Abbreviations ACT Activating group ACTH Adrenocorticotropic hormone ACYP Acylphosphatase-2 Ade Adenine CAS Chemical Abstracts Service CBT 2-Cyanobenzothiazole CDI Carbonyldiimidazole Cpa m -Cyanopyridyl-alanine CuAAC Copper(i)-catalysed azidealkyne cycloaddition DBMB 2,4-Dibromo-5-methoxybenzaldehyde Dbz Diaminobenzoic acid DEBPT (3-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3 H )-one) DFS Decafluoro-diphenylsulfone DIPEA N , N -Diisopropylethylamine DKP Diketopiperazine DMF Dimethyl formamide DPPA Diphenyl phosphoryl azide fAr Perfluoroarenes FDA Food and Drug Administration GFP Green fluorescent protein GII Second generation Grubbs' catalyst HEPES N -2-Hydroxyethylpiperazine- N -2-ethanesulfonic acid HATU Hexafluorophosphate azabenzotriazole tetramethyl uronium HBTU Hexafluorophosphate benzotriazole tetramethyl uronium HCTU 2-(6-Chloro-1 H -benzotriazole-1-yl)-1,1,3,3-tetramethylaminium hexafluorophosphate HMGA1a High-mobility group protein HOBt Hydroxybenzotriazole IL-25 Interleukin 25 -KAHA Alpha-ketoacid-hydroxylamine KaY/KaR Lysineformaldehydetyrosine/lysineformaldehydearginine MeNbz N -Methyl benzotriazole MOrPH-PhD Macrocyclic organo-peptide hybrid phage display MUC1 Mucin 1 NCL Native chemical ligation NMP N -Methyl-2-pyrrolidone O2beY o -(2-Bromomethyl)tyrosine OPA o -Phthalaldehyde PEG Polyethylene glycol RaPID Random nonstandard peptide integrated discovery RCM Ring closing metathesis RNA Ribonucleic acid SiaNAz N -Azidoacetyl sialic acid SICLOPPS Split-intein circular ligation of peptides and proteins SPAAC Strain-promoted azidealkyne cycloaddition SPhR Staudinger phosphonite reaction SPPS Solid phase peptide synthesis STL Serine/threonine ligation TAMM 2-((Alkylthio)(aryl)methylene)malononitrile TeTEx Tetrazinethiol exchange TCEP Tris(2-carboxyethyl)phosphine Supplementary Material Acknowledgments We thank the Australian Research Council for funding support, including a Discovery Project (DP230100079) and Future Fellowship (FT220100010) awarded to CN

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