Peptides and aptamers for targeting of neuron or nerves
The present invention provides methods for guiding preservation of neurons or nerves during surgery by administering a fluorescently-labeled peptide or aptamer that specifically binds to the neurons or nerves. The invention further provides targeting molecules of fluorescently-labeled peptides or aptamers that specifically bind to neurons or nerves and for compositions thereof.
1. A targeting molecule comprising a peptide that specifically binds to a peripheral nervous system (PNS) neuron or nerve, or component of either, wherein the peptide is at least 85% homologous to a peptide comprising NTQTLAKAPEHT (SEQ ID NO:4).
2. The molecule of claim 1 , further comprising a drug.
3. The molecule of claim 1 , further comprising a drug selected from the group consisting of: an antihistamine, a GABA receptor modulator, a neurotransmitter reuptake inhibitor, a local anesthetic, an anticholinergic, a sodium channel blocker, a calcium channel blocker, a thyrotropin-releasing hormone, a y-secretase inhibitor, an AMPA receptor agonist or antagonist, an NMDA receptor agonist or antagonist, an mGlu receptor agonist or antagonist, a growth factor, an antiemetic agent, a corticosteroid; a cytotoxic agent; an antioxidant, an iron chelator, a mitochondrial modulator, a sirtuin modulator, a nitric oxide (NO) and/or nitric oxide synthase (NOS) modulator, a potassium channel agonist or antagonist, a purigenic receptor agonist or antagonist and combinations thereof.
4. The molecule of claim 1 , further comprising a drug selected from the group consisting of: benzocaine, cardcaine, cinchocaine, cyclomethycaine, lidocaine, pritocaine, propxycaine, proparacaine, tetracaine, tocainide, trimecaine, methotrexate, cyclophosphamide, thalidomide, paclitaxel, pemetrexed, pentostatin, pipobroman, pixantrone, plicamycin, procarbazine, raltitrexed, rebeccamycin, rubitecan, SN-38, salinosporamide A, satraplatin, streptozotocin, swainsonine, tariquidar, taxane, tegafur-uracil, temozolomide, testolactone, thioTEPA, tioguanine, topotecan, trabectedin, tretinoin, triplatin tetranitrate, tris(2-chloroethyl)amine, troxacitabine, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, vorinostat, zosuquidar, carbamazepine, oxcarbazepine, phenytein, valproic acid, sodium valproate, cinnarizine, flunarizine, nimodipine, brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), gilal cell-line derived neurotrophic factor (GDNF), neurotrophin-3, neurotrophin-4, fibroblast growth factor (FGF) receptor, insulin-like growth factor (IGF) and combinations thereof.
5. The molecule of claim 1 , further comprising a fluorescent moiety.
6. The molecule of claim 1 , further comprising a fluorescent moiety selected from the group consisting of: a fluorescent dye, a fluorescent peptide, a fluorescent dye and combination thereof.
7. The molecule of claim 1 , further comprising a fluorescent moiety selected from the group consisting of: a xanthene a bimane a coumarin an aromatic amines a benzofuran a fluorescent cyanine a carbazole a dicyanomethylene pyrane polymethine oxabenzanthrane pyrylium carbostyl perylene acridone quinacridone rubrene anthracene coronene phenanthrecene pyrene butadiene stilbene porphyrin pthalocyanine lanthanide metal chelate complexes and rare-earth metal chelate complexes.
8. The molecule of claim 1 , further comprising a fluorescent moiety selected from the group consisting of: 5-carboxyfluorescein, fluorescein-5-isothiocyanate, 6-carboxyfluorescein, tetramethylrhodamine-6-isothiocyanate, 5-carboxytetramethylrhodamine 5-carboxy rhodol derivatives tetramethyl and tetraethyl rhodamine diphenyldimethyl and diphenyldiethyl rhodamine dinaphthyl rhodamine; rhodamine 101 sulfonyl chloride Cy3, Cy3B, Cy3.5, Cy5, Cy5˜5, Cy 7, indocyanine green, IRS00CW and combinations thereof.
9. A method of identifying a PNS neuron or nerve, comprising contacting the PNS neuron or nerve with a targeting molecule comprising (a) a peptide that specifically binds to the neuron or nerve, or component of either, and (b) a fluorescent moiety, wherein the peptide is at least 85% homologous to a peptide comprising NTQTLAKAPEHT (SEQ ID NO:4).
10. The method of claim 9 , wherein the fluorescent moiety selected from the group consisting of: a fluorescent dye, a fluorescent peptide, a fluorescent dye and combinations thereof.
11. The method of claim 9 , wherein the fluorescent moiety selected from the group consisting of: a xanthene a bimane a coumarin an aromatic amines a benzofuran a fluorescent cyanine a carbazole a dicyanomethylene pyrane polymethine oxabenzanthrane pyrylium carbostyl perylene acridone quinacridone rubrene anthracene coronene phenanthrecene pyrene butadiene stilbene porphyrin pthalocyanine lanthanide metal chelate complexes and rare-earth metal chelate complexes.
12. The method of claim 9 , wherein the fluorescent moiety selected from the group consisting of: 5-carboxyfluorescein, fluorescein-5-isothiocyanate, 6-carboxyfluorescein, tetramethylrhodamine-6-isothiocyanate, 5-carboxytetramethylrhodamine 5-carboxy rhodol derivatives tetramethyl and tetraethyl rhodamine diphenyldimethyl and diphenyldiethyl rhodamine dinaphthyl rhodamine rhodamine 101 sulfonyl chloride Cy3, Cy3B, Cy3.5, Cy5, Cy5˜5, Cy 7, indocyanine green, IRS00CW and combinations thereof.
13. A method of delivering a drug to a PNS neuron or nerve, comprising contacting the PNS neuron or nerve with a targeting molecule comprising (a) a peptide that specifically binds to the neuron or nerve, or component of either, and (b) a drug, wherein the peptide is at least 85% homologous to a peptide comprising NTQTLAKAPEHT (SEQ ID NO:4).
14. The method of claim 13 , wherein the drug is selected from the group consisting of: an antihistamine, a GABA receptor modulator, a neurotransmitter reuptake inhibitor, a local anesthetic, an anticholinergic, a sodium channel blocker, a calcium channel blocker, a thyrotropin-releasing hormone, a y-secretase inhibitor, an AMPA receptor agonist or antagonist, an NMDA receptor agonist or antagonist, an mGlu receptor agonist or antagonist, a growth factor, an antiemetic agent, a corticosteroid; a cytotoxic agent; an antioxidant, an iron chelator, a mitochondrial modulator, a sirtuin modulator, a nitric oxide (NO) and/or nitric oxide synthase (NOS) modulator, a potassium channel agonist or antagonist, a purigenic receptor agonist or antagonist and combinations thereof.
15. The method of claim 13 , wherein the drug is selected from the group consisting of: benzocaine, cardcaine, cinchocaine, cyclomethycaine, lidocaine, pritocaine, propxycaine, proparacaine, tetracaine, tocainide, trimecaine, methotrexate, cyclophosphamide, thalidomide, paclitaxel, pemetrexed, pentostatin, pipobroman, pixantrone, plicamycin, procarbazine, raltitrexed, rebeccamycin, rubitecan, SN-38, salinosporamide A, satraplatin, streptozotocin, swainsonine, tariquidar, taxane, tegafur-uracil, temozolomide, testolactone, thioTEPA, tioguanine, topotecan, trabectedin, tretinoin, triplatin tetranitrate, tris(2-chloroethyl)amine, troxacitabine, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, vorinostat, zosuquidar, carbamazepine, oxcarbazepine, phenytein, valproic acid, sodium valproate, cinnarizine, flunarizine, nimodipine, brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), gilal cell-line derived neurotrophic factor (GDNF), neurotrophin-3, neurotrophin-4, fibroblast growth factor (FGF) receptor, insulin-like growth factor (IGF) and combinations thereof.
16. A pharmaceutical composition comprising: (a) a peptide that specifically binds to a PNS neuron, nerve, or component of either, and (b) a pharmaceutically acceptable excipient, wherein the peptide is at least 85% homologous to a peptide comprising NTQTLAKAPEHT (SEQ ID NO:4).
17. The composition of claim 16 , wherein the peptide is bound to a drug or fluorescent moiety.