Table 2.
Studies demonstrating neuroprotective and other neuroactive properties of peptides fused to TAT and other cell penetrating peptides.
| Peptide name | Peptide sequence | % Arginine | Net charge at pH 7 | Neuronal injury model | References |
|---|---|---|---|---|---|
| TAT-NR2B9c (NA-1) | YGRKKRRQRRR-KLSSIESDV | 30% | +7 | Excitotoxicity, stroke, HIE, ICH, AD, epilepsy, pain | (59–68) |
| JNKI-1D-TAT, JNKI-1-TAT | dqsrpvqpflnlttprkprpp-rrrqrrkkrg-NH2, GRKKRRQRRR-PP-RPKRPTTLNLFPQVPRSQD-NH2 |
29% | +12 | Excitotoxicity, stroke, HIE, ICH, TBI, AD, SCI, SMA, epilepsy, pain | (60, 69–83) |
| TAT-JIP-1 | GRKKRRQRRR-RPKRPTTLNLF | 38% | +11 | Excitotoxicity, stroke, GCI, PD | (84–86) |
| δSV1-1-TAT | YGRKKRRQRRR-SFNSYELGSL | 28% | +7 | Stroke | (87, 88) |
| TAT-JBD | GRKKRRQRRR-PP-RPKRPTTLNLFPQVPRSQDT | 28% | +11 | HIE, GCI | (89, 90) |
| TAT-NPEG4-(IETDV)2 | YGRKKRRQRRR-(Peg)4-(IESDV)2 | 28% | +9 | Stroke, pain, epilepsy, cortical spreading depression | (91–95) |
| JNK3-N-TAT | YGRKKRRQRR-RCSEPTLDVKI | 29% | +6.9 | PD | (96, 97) |
| Src40–49Tat | KPASADGHRGY-GRKKRRQRRR | 33% | +9.1 | Pain | (98) |
| TAT-SabKIM1 | GFESLSVPSPLDLSGPRVVAPP-RRRQRRKKRG-NH2 | 22% | +8 | PD | (99) |
| TAT-CBD3 | YGRKKRRQRRR-ARSRLAELRGVPRGL | 38% | +11 | Excitotoxicity, stroke, TBI, pain | (100–105) |
| R9-CBD3 | RRRRRRRRR-ARSRLAELRGVPRGL | 54% | +12 | ||
| TAT-CBD3A6K | YGRKKRRQRRR-ARSRLKELRGVPRGL | 38% | +12 | ||
| TAT-CRMP-2 | YGRKKRRQRR-GVPRGLYDGVCEV | 26% | +6.9 | Excitotoxicity, stroke, OGD | (106–108) |
| TAT-NR2Bct | YGRKKRRQRRR-KKNRNKLRRQHSY | 37% | +14.1 | Excitotoxicity, stroke | (109–111) |
| TAT-NR2Bcts | YGRKKRRQRRR-NRRRNSKLQHKKY | 35% | +14.1 | Excitotoxicity | (109, 110) |
| Tat-D2LIL3−29−2 | YGRKKRRQRRR-MKSNGSFPVNRRRMD | 34% | +11 | Depression | (112) |
| Penetratin-COG133 (COG112) | Ac-RQIKIWFQNRRMKWKK-LRVRLASHLRKLRKRLL-NH2 | 24% | +14.1 | TBI, EAE, AD, axonal regeneration, spinal cord demyelination | (40, 41, 47, 113–115) |
| TAT-NR2Bct-CTM | YGRKKRRQRRR-KKNRNKLRRQHSY-KFERQKILDQRFFE | 35% | +15.1 | Stroke | (116) |
| CN2097 | RRRRRRRC-s-s-CKNYKKTEV (cyclic or linear) | 41% | +9 | Excitotoxicity, pain | (14, 117) |
| P42-TAT | AASSGVSTPGSAGHDIITEQPRS-GG-YGRKKRRQRRR | 19% | +7.1 | Huntington's disease | (118) |
| TAT-p53DM | YGRKKRRQRRR-RVCACPGRDRRT | 43% | +11 | 288,289 | (14, 109, 119, 120) |
| TAT-p53DMs | YGRKKRRQRRR-CCPGECVRTRRR | 43% | +11 | Excitotoxicity | (109) |
| TAT-CN21 | YGRKKRRQRR-KRPPKLGQIGRSKRVVIEDDR | 29% | +11 | Excitotoxicity, stroke, GCI | (121–123) |
| PYC36-TAT, PYC36D-TAT |
GRKKRRQRRRGG-LQGRRRQGYQSIKP, pkisqygqrrrgqlgg-rrrqrrkkrg |
35% | +12 | Excitotoxicity | (10) |
| TAT-GluR6-9c | YGRKKRRQRR-RLPGKETMA | 32% | +8 | Excitotoxicity, GCI, stroke, OGD | (124–126) |
| TAT-mGluR1 | YGRKKRRQRRR-VIKPLTKSYQGSGK | 24% | +11 | Excitotoxicity, HIE, SAH | (127–129) |
| TAT-K13 | YGRKKRRQRR-KEIVSRNKRRYQED | 33% | +9 | Stroke | (130) |
| TAT-Indip | YGRKKRRQRRR-GEPHKFKREW | 33% | +9.1 | Excitotoxicity, ALS | (109, 131) |
| TAT-Indip-K/R | YGRKKRRQRRR-GEPHRFRREW | 43% | +9.1 | Excitotoxicity | (109) |
| TAT-GESV, D-TAT-GESV |
RRRQRRKKRG-YAGQWGESV, rrrqrrkkrg-yagqwgesv |
32% | +7 | Excitotoxicity, HIE, pain | (132–134) |
| TAT-NEP1-40 | YGRKKRRQRRR-RIYKGVIQAIQKSDEGHPFRAYLESEV AISEELVQKYSNS | 16% | +7.1 | Stroke, OGD | (135, 136) |
| TAT-NBD | YGRKKRRQRRR-TALDWSLWQTE | 27% | +6 | HIE | (137) |
| TAT-ψεHSP90 | YGRKKRRQRRR-PKDNEER | 39% | +8 | Stroke, OGD | (138) |
| TAT-Bec | YGRKKRRQRRR-GG-TNVFNATFEIWHDGEFGT | 19% | +6.1 | SCI | (139) |
| TAT-gp91ds | GRKKRRQRRR-CSTRIRRQL-NH2 | 47% | +12 | SCI, TBI, SAH | (140–142) |
| TAT-ISP | GRKKRRQRRR-CDMAEHMERLKANDSLKLSQEYESI-NH2 | 20% | +6 | SCI | (143) |
| Tat-Cav3.2-III-IV | YGRKKRRQRRR-EARRREEKRLRRLERRRRKAQ | 50% | +16 | Pain | (144) |
| TAT-μCL | YGRKKRRQRRR-PPQPDALKSRTLR | 33% | +10 | Retinal degeneration | (145) |
| ST2-104 | RRRRRRRRR-ARSRLAELRGVPRGL | 54% | +12 | Pain | (146) |
| TAT-STEP | YGRKKRRQRRR -GLQERRGSNVSLTLDM | 30% | +8 | Excitotoxicity, stroke, OGD | (147) |
| TAT-K | YGRKKRRQRRR-PP-LNRTPSTVTLNNNT | 26% | +9 | Excitotoxicity | (148) |
| TAT-P110 | YGRKKRRQRRR-GG-DLLPRGT | 35% | +9 | Stroke, Huntington's disease | (149, 150) |
| TAT-C6 | GRKKRRQRRR-CRRGGSLKAAPGAGTRR | 37% | +14 | Stroke | (151) |
| Analog 4 and 5 | Y-βP-WFGG-RRRRR, YaWFGG-RRRRR | 45% | +5 | Pain | (152) |
| Aβ1-6A2VTAT(D) | grkkrrqrrr-gggg-dvefrh | 35% | +8.1 | AD | (153) |
| DEETGE-CAL-TAT | RKKRRQRRR-PLFAER-LDEETGEFLP-NH2 | 28% | +5 | GCI | (154) |
| TAT-T406 | RKKRRQRR-IAYSSSETPNRHDML | 29% | +7.1 | Pain | (155) |
| TAT-21-40 | RKKRRQRRR-RIPLSKREGIKWQRPRFTRQ | 38% | +14 | Excitotoxicity, stroke, OGD | (156) |
| TAT-C1aB | YGRKKRRQRRR-HLSPNKWKW | 30% | +10.1 | Excitotoxicity, stroke | (157) |
| TAT-2ASCV | YGRKKRRQRRR-TVNEKVSC | 31% | +8 | Pain | (158) |
| TAT-NTS | YGRKKRRQRRR-RSFPHLRRVF-NH2 | 43% | +12.1 | Stroke, OGD | (159) |
| TAT-CBD3M5L | YGRKKRRQRR-ARSRMA | 44% | +9 | Pain | (160) |
| TDP-r8 | YrFG-rrrrrrrr-G | 69% | +9 | Pain | (161) |
| TAT-Pro-ADAM10 | YGRKKRRQRR-PKLPPPKPLPGTLKRRRPPQP | 27% | +14 | Huntington's disease | (162) |
At the N-terminus, Ac indicates acetyl and at the C-terminus NH2 indicates amide. Lower case single letter code indicates D-isoform of the amino acid. Aib, 2-Aminoisobutyric acid or 2-methylalanine; s-s, disulfide bond; AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; EAE, Experimental autoimmune encephalomyelitis; GCI, global cerebral ischaemia; HIE, hypoxia-ischaemia encephalopathy; ICH, intracerebral hemorrhage; OGD, oxygen glucose deprivation; PD, Parkinson's disease; SAH, subarachnoid hemorrhage; SCI, spinal cord injury; SMA, spinal muscular atrophy; stroke, ischaemic stroke; TBI, traumatic brain injury.