Table 1.

Engineered cyclotides from the trypsin inhibitor and Möbius subfamilies with novel biological activities. Table adapted and updated from references [11,23].

Cyclotide	Biological Activity	Loop	Application	Reference
Modified
Trypsin inhibitor subfamily
MCoTI-I	Antibacterial	6	Broad-spectrum antibacterial	[97]
MCoTI-I	MAS1 receptor	6	Lung cancer and myocardial	[35]
	agonist		infarction
MCoTI-II	b-factor XIIa inhibitor	1 & 5	Antithrombotic	[98]
MCoTI-II	KLK4 inhibitor	1 & 8	Anti-cancer	[99]
MCoTI-I	CXCR4 antagonist	6	Anti-metastatic and anti-HIV PET-CT imaging	[33,34,66]
MCoTI-II	Antiangiogenic	5 & 6	Anti-cancer	[100]
MCoTI-II	SET antagonist	6	Potential anticancer	[101]
MCoTI-II	CTLA-4 antagonist	1, 3 & 6	Immunotherapy for cancer	[102]
MCoTI-II	BCR-Abl kinase	1 & 6	Chronic myeloid leukemia	[103]
	Inhibitor
MCoTI-I	p53-Hdm2/HdmX	6	Anti-cancer	[5]
	Antagonist		pathway
MCoTI-II	Tryptase inhibitor	1	Anti-cancer	[48]
MCoTI-II	Thrombospondin-1 (TSP-1)	6	Microvascular endothelial	[104]
	agonist		cell migration inhibition
			anti-angiogenesis
MCoTI-II	VEGF receptor agonist	6	Cardiovascular damage	[105]
			and wound healing
MCoTI-II	β-Tryptase inhibitor	3, 5 & 6	Inflammation diseases	[106]
MCoTI-II	β-Tryptase inhibitor	1	Inflammation diseases	[107]
	Human elastase inhibitor
MCoTI-II	FMDV 3C protease	1	Anti-viral for FMDV	[68]
	Inhibitor
MCoTI-I	α-Synuclein-induced cytotoxicity inhibitor	6	Parkinson’s disease	[74]
M öbius subfamily
Kalata B1	Immunomodulator	4	Protecting against multiple Sclerosis	[31]
Kalata B1	Immunomodulator	5 & 6	Protecting against multiple	[108]
			sclerosis
Kalata B1	Neuropilin-1/2 antagonist	5 & 6	Inhibition of endothelial cell migration and angiogenesis	[109]
Kalata B1	Bradykinin B1 receptor antagonist	6	Chronic and inflammatory pain	[30]
Kalata B1	Melanocortin 4 receptor Agonist	6	Obesity	[110]
Kalata B1	Dengue NS2B-NS3 protease inhibitor	2 & 5	Anti-viral for Dengue virus infections	[111]
Kalata B1	VEGF-A antagonist	2, 3, 5 & 6	Anti-angiogenic, potential anti-cancer activity	[112]