Lipidization as a tool toward peptide therapeutics

Figures & data

Figure 1. Examples of peptide lipidization; GlcN: glukoseamine; GPI: glypiation, ins: inositol; man: mannose; PE: phosphatidylethanolamine. Note: the figure was drawn by the authors.

Figure 2. Structure of linkers used for peptide lipidization; (a) γ-glutamyl linker, (b) OEG-OEG, (c) gamma-aminobutyric linker, (d) TTDS linker, (e) 8-amino-3,6-dioxactanoic acid. Note: the figure was drawn by the authors.

Table 1. Currently approved lipidized peptide-based therapeutics.

Drug	Type of modification	Parental molecule	Indication	Routes of administration	Reference
Liraglutide	Acylation	GLP-1	T2DM	s.c. injection	Iepsen et al. (2015)
			Obesity	s.c. injection	NovoNordisk (2020)
Semaglutide	Acylation	GLP-1	T2DM	s.c. injection Oral	Scheen (2020)
			Obesity	s.c. injection	FDA (2021)
Detemir	Acylation	Insulin	Diabetes	s.c. injection	Home and Kurtzhals (2006)
Degludec	Acylation	Insulin	Diabetes	s.c. injection	Jarosinski et al. (2021)
Xultophy	Acylation	Insulin + GLP-1	T2DM	s.c. injection	Steyn (2022)
Somapacitan	Acylation	Human growth hormone	Growth hormone deficiencies	s.c. injection	FDA (2020)
Tesamorelin	Acylation	Human growth hormone releasing hormone	HIV-associated lipodystrophy	s.c. injection	Stanley et al. (2019)
Tirzepatide	Acylation	GLP-1/GIP	T2DM	s.c. injection	Syed (2022)
Mifamurtide	PE-anchor attachment + acylation	Muramyl dipeptide	Osteosarcoma	i.v. injection	Frampton (2010)
Polymyxin B	Acylation		Bacterial infection	i.v. injection/inhalation/topical	Moffatt et al. (2019)
Daptomycin	Acylation		Bacterial infection	i.v. injection	Heidary et al. (2017)

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