Beyond canonical PROTAC: biological targeted protein degradation (bioTPD)

Biomaterials Research

Table 2 Representative example of peptide-based bioTPD

Pathway	Adaptor	Key sequences	POI	POI ligands	Refs
Proteasome	VHL	MLAP(OH)YIPM	METAP2 ER	Fumagillo Estradiol	[60]
		LAP(OH)YI	AR ER CREPT	Dihydrotestosterone Estradiol VRALKQKYEELKKEKESLVDK	[100, 104]
		ALAPYIP	Akt FRS2α PI3K Tau	Recognition peptide for Akt2 (P-ser474) IENPQYFSDA GPGGDYAAMGACPASEQGYEEMRA YQYQDATADEQG	[109, 110, 114]
	β-TRCP	DRHDS(P)GLDS(P)M	METAP2	Ovalicin	[11]
	KEAP1	LDPETGEYL	Tau	YQYQDATADEQG	[118]
	/	RRRG	α-synuclein	GVLYVGSKTR	[136]
Lysosome	/ / /	KFERQKILDQRFFE MDFSGLSLIKLKKQ cyclic RGDyK	DAPK1 α-synuclein PD-L1 PD-L1	A fragment of the GluN2B subunit A short peptide of β-synuclein DKEMAATSAAIEDAVRRIEDMMNQ BMS-8	[24] [131] [132]

Abbreviations: VHL, Von Hippel-Lindau; METAP2, Methionine aminopeptidase 2; ER, Estrogen receptor; AR, Androgen receptor; CREPT, Cell cycle-related and expression-elevated protein in tumor; Akt, Serine/threonine-protein kinase AKT; FRS2α, Factor receptor substrate 2α; PI3K, Phosphatidylinositol-3-kinase; Tau, microtubule-associated protein; α-synuclein, alpha-synuclein; DAPK1, Death associated protein kinase 1; PD-L1, programmed cell death ligand 1

ISSN: 2055-7124