A Heparan Sulfate-Binding Cell Penetrating Peptide for Tumor Targeting and Migration Inhibition

Table 1

pI, sequence, and structures of HS-binding cell penetrating peptides.

	Peptide name; pI	Sequence and predicted secondary structure^*	Heparan sulfate binding region	Internalization mechanism	Ref.
	Viral protein-derived CPP
1	TAT peptide (49–57); pI: 12.70	RKKRRQRRR; CCCCCCCCC	RKKRRQRR	Lipid raft-mediated macropinocytosis	[25, 26]
2	Nucleoplasmin NLS (155–170); pI: 11.47	KRPAAIKKAGQAKKKK; CcHHHHHHHhHHHhCC	Not reported	Not reported	[58]
3	HTLV-II Rex (4–16); pI: 12.85	TRRQRTRRARRNR; CCCCHHHHCCCCC	TRRQRT	Direct translocation	[21, 22]
4	Lambda-N (48–62); pI: 11.83	QTRRRERRAEKQAQW; CCHHHHHHHHHHCCC	RRRERR	Not reported	[22]
5	Phi21 N (12–29); pI: 11.45	TAKTRYKARRAELIAERR; CCCCCCCHHHHHHHHHHH	KTRYKARRA	Not reported	[22]
6	Delta N (1–22); pI: 11.44	MDAQTRRRERRAEKQAQWKAAN; CCCCHHHHHHHHHHHHHHHHHH	TRRRERRA	Not reported	[22]
7	FHV coat (35–49); pI: 13.00	RRRRNRTRRNRRRVR; CCCCCCCCCCCCCCC	RRRRNRTRRNRRRVR	Not reported
8	BMV coat (8–26); pI: 12.78	KMTRAQRRAAARRNRWTAR; CcCHHHHHHHHHHhccccC	ARRNRW	Not reported
9	HIV-1 Rev (35–46); pI: 12.85	RQARRNRRRRWR; CCCCCCCHHHHH	RQARRNRRRRWR	Not reported	[22]
10	Rev (26–42); pI: 12.54	TRQARRNRRRRWRERQF; CCCCCCCCHHHHHHHHH	TRQARRNRRRRWRERQF	Energy dependent lipid raft-mediated macropinocytosis	[27, 28]
11	CPP from pestivirus envelope glycoprotein (Erns) (194–220); pI: 11.72	ENARQGAARVTSWLGRQLRIAGKRLEGRSKTWFGAYA; CCCccchHHHHHHHHHHHHHHHHhhhCCCCccccccC	Basic residues	Direct translocation	[23]
12	gp41 fusion sequence; pI: 11.33	GALFLGWLGAAGSTMGAWSQPKKKRKV; HHHHHHHHHHHHHHHHHCCCCCCCCCC	WSQPKKKRKV	Direct translocation	[24]
13	VP22; pI: 12.10	DAATATRGRSAASRPTERPRAPARSASRPRRPVD; CCCccCCCCCCCCCCCCCCCCCCCCCCCCCCCCC	SRPRRP	Energy dependent lipid raft-mediated macropinocytosis	[27, 29]
14	SV40 NLS; pI: 11.33	PKKKRKV; CCCCCCC	PKKKRKV	Not reported	[59, 60]
	Animal homeostatic modulator-derived CPP
15	Penetratin; pI: 12.31	RQIKIWFQNRRMKWKK; CCCHHHHHHHCCCCCC	NRRMKW	Direct translocation; Endocytosis	[61]
16	CPPecp; pI: 10.05	NYRWRCKNQN; CCCCCCCCCC	RWRCK	Macropinocytosis	[12, 62]
17	Apolipoprotein B binding domain; pI: 9.82	SVKAQYKKNSDKHRLMRKRGLK; CCcccccCCCCCCCCCCcCCCC	Basic residues	Endocytosis	[63, 64]
18	hCT (932); pI: 6.74	LGTYTQDFNKFHTFPQTAIGVGAP; HHHHHHHHHHHHHHCHHHHHCCCC	Not reported	Endocytosis	[63, 65]
19	pVEC; (615–632); pI: 12.48	LLIILRRRIRKQAHAHSK; ChhHHHHHHHHHHHhcCC	LRRRIRK	Macropinocytosis and clathrin mediated endocytosis	[66–68]
20	hLF peptide; pI: 10.93	KCFQWQRNMRKVRGPPVSCIKR; CCCchhHHHHhCCCCCcececC	MRKVRG	Lipid raft-mediated endocytosis	[69]
21	PDX-1-PTD; pI: 12.31	RHIKIWFQNRRMKWKK; ChhhhHhhhhhhhhcC	NRRMKWKK	Caveolae-dependent endocytosis and lipid raft-mediated macropinocytosis	[70]
	Antimicrobial peptide
22	LL-37 (1–37); pI: 10.61	LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES; HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHCCCCC	FRKSKEKI	Endocytosis	[30, 31, 71]
23	SynB1 (1–18); pI: 12.30	RGGRLSYSRRRFSTSTGR; CCCCEEEEECCEEEEECC	Basic residues	Endocytosis	[32]
24	SynB3; pI: 12.18	RRLSYSRRRF; CCCCcccCCC	Basic residues	Endocytosis	[32]
	Toxin-derived CPP
25	bPrPp (1–28); pI: 10.03	MVKSKIGSWILVLFVAMWSDVGLCKKRP; CCCCCCCCHHHHHHHHHHHHHHHCCCC	Basic residues	Macropinocytosis	[33]
26	Crotamine (1–42); pI: 9.51	YKQCHKKGGHCFPKEKICLPPSSDFGKMDCRWRWKCCKKGSG; CCHHHHHCEEEECCCCCCCCCCCEECCCCCCCCCEEEECCCC	RWRWK	Endocytosis	[34]
27	Maurocalcine (MCa) (1–33); pI: 9.46	GDCLPHLKLCKENKDCCSKKCKRRGTNIEKRCR; CCCCCCCCCCCCHHHCCCCEEECCCCCCCCEEE	SKKCKR and EKRCR	Macropinocytosis	[35, 36]

The confidence of the prediction is denoted by scaling the predictions from week (lower-case letter) to strong (upper-case letter). “H,” “E,” and “C” refer to α-helical, β-strand, and random coil propensities, respectively.