Table 2.

Examples of peptides from insect (honey bee and wasp) venom and derivatives with cell penetrating property.

Peptide	Sequence a	Size	Major Structural Features b	Mechanism(s) of Cell Penetration c	Cargo Delivery d	Ref.
Honey bee
Mellitin (MEL)	GIGAVLKVLTTGLPALISWIKRKRQQ-NH2	26	Amphipathic α-helix	DT, PF	FD	[49]
Tat/CM18 hybrid			Chimera	DT, MD, ND	CI	[52]
MEL-d(KLAKLAK)2	GIGAVLKVLTTGLPALISWIKRKRQQGGGGS-d[KLAKLAKKLAKLAK]	45	Chimera	DT (?)	AP	[53]
p5RHH	VLTTGLPALISWIRRRHRRHC	21	C-terminal fragment	Endocytosis (?)	DNA polyplexes	[54,55]
p5RWR	VLTTGLPALISWIKRKRQQRWRRRR	25	C-terminal fragment	Endocytosis (?)	DNA polyplexes	[54,55]
MT20	GIGAVLKVLTTGLPALISWI	20	Hydrophobic helix	DT, MD	DNA polyplexes	[56]
FL20	GIGAILKVLATGLPTLISWI	20	Hydrophobic helix	DT, MD	DNA polyplexes	[56]
Melittin [1,2,3,4,5,6,7,8,9,10,11,12,13,14]	GIGAVLKVLTTGLP	14	N-terminal fragment	DT	NC, LP	[57]
Wasp
Anoplin	GLLKRIKTLL-NH2	10	Amphipathic α-helix	DT, PF	FD	[60]
Anoplin dimer	(GLLKRIKTLL-NH2)2	20	C-N terminal dimer	DT, PF	-	[61]
Mastoparan	INLKALAALAKKIL-NH2	14	Amphipathic α-helix	DT, PF	-	[64]
Mastoparan-X	INWKGIAAMAKKLL-NH2	14	Amphipathic α-helix	DT, PF	-	[65]
Transportan	GWTLNSAGYLLGKINLKALAALAKKIL-NH2	27	Chimera	multiple	CI	[66]
TP10	AGYLLGKINLKALAALAKKIL-NH2	21	Shorter transportan	multiple	CI	[70,77]
TP10-5	AGYLLGKINLKKLAKL(Aib)KKIL-NH2	21	Helical stabilized	DT	FD	[71]
Transportan 9dR	GWTLNSAGYLLGKINLKALAALAKKIL(dR)9	36	Chimera	Endocytosis (?)	siRNA	[73]
Mitoparan	INLKKLAKL(Aib)KKIL-NH2	14	Mastoparan analogue	DT	FD, AP	[78,79,80]

Notes: ^a-NH2, amidated peptide; anoplin C-N terminal dimer, as prepared by intermolecular triazole bridge; Aib, α-aminoisobutyric acid; ^b Particular structural characteristics of native, designed or analogous peptides; C-N terminal dimer, intermolecular dimerization involving the carboxyl-terminus of one peptide and the amino-terminus of the other; ^c DT, direct translocation; PF, pore forming; MD, membrane-disruptive cell uptake; NR, non-disruptive penetration; RM, receptor-mediated endocytosis; HI, hydrophobic insertion; multiple, more than a single mechanism of cell entry, that can involve direct translocation and endocytosis; ^d FD, fluorescent dyes; CI, diverse types of cell impermeant cargoes; AP, apoptotic peptides; NC, nanocrystals; LP, large proteins; RD, radionuclides; EZ, enzymes; IR, infrared; “-,” not applicable.