The present invention provides composition comprising one or more glycosaminoglycan mimetics and uses thereof. The subject glycosaminoglycan mimetics are particularly useful for treatment of neuronal injuries including without limitation spinal cord injuries.
대표청구항▼
1. A sulfated glycosaminoglycan mimetic polymer having a plurality of repeating subunits, wherein an individual repeating subunit of said repeating subunits is a saccharide covalently linked to a backbone, wherein the number of repeating subunits in said polymer is m, and wherein the sulfated glycos
1. A sulfated glycosaminoglycan mimetic polymer having a plurality of repeating subunits, wherein an individual repeating subunit of said repeating subunits is a saccharide covalently linked to a backbone, wherein the number of repeating subunits in said polymer is m, and wherein the sulfated glycosaminoglycan mimetic polymer is of a formula: or or a pharmaceutically acceptable salt or ester thereof; wherein R1, R2, R3, and R4 are each independently selected from the group consisting of hydroxyl, sulfate, and phosphate;one or more of R1, R2, R3, and R4 is a sulfate;R6 is selected from the group consisting of hydrogen, sulfite and acetyl;n is 1 or greater;wherein n1 is between 1 and 25, n2 is between 1 and 10, n3 is between 1 and 10;and m is 2 or greater. 2. The polymer of claim 1, wherein: (a) R1 and R2 are each independently selected from sulfate and phosphate; and R3 and R4 are hydroxyl;(b) R3 and R4 are each independently selected from sulfate and phosphate; and R1 and R2 are hydroxyl;(c) R1, R2, and R3 are each independently selected from sulfate and phosphate; and R4 is hydroxyl;(d) R1, R2, and R4 are each independently selected from sulfate and phosphate; and R3 is hydroxyl;(e) R2, and R4 are each independently selected from sulfate and phosphate; and R1, and R3 are hydroxyl;(f) R1 is sulfate; and R2, R3, and R4 are hydroxyl;(g) R2 is sulfate; and R1, R3, and R4 are hydroxyl;(h) R3 is sulfate; and R1, R2, and R4 are hydroxyl;(i) R4 is sulfate; and R1, R2, and R3 are hydroxyl;(j) R1 and R3 are each independently selected from sulfate, and phosphate; and R2, and R4 are hydroxyl;(k) R1 and R4 are each independently selected from sulfate, and phosphate; and R2, and R3 are hydroxyl; or(l) R2 and R4 are each independently selected from sulfate and phosphate; and R1, and R3 are hydroxyl;and whereinR6 is selected from the group consisting of sulfite and acetyl. 3. The polymer of claim 1, wherein n is 10 or greater. 4. The polymer of claim 1, wherein n is 25 or greater. 5. The polymer of claim 1, wherein n is between 1 and 25. 6. The polymer of claim 1, wherein n is 1. 7. The polymer of claim 1, wherein n is 2. 8. The polymer of claim 1, wherein m is 5 or greater. 9. The polymer of claim 1, wherein m is 25 or greater. 10. The polymer of claim 1, wherein m is 50 or greater. 11. The polymer of claim 1, wherein m is 100 or greater. 12. The polymer of claim 1, wherein m is between 2 and 100. 13. A pharmaceutical composition comprising a polymer of claim 1 and a pharmaceutically acceptable carrier or excipient. 14. A composition comprising a population of the polymer of claim 1. 15. The composition of claim 14, wherein the composition has a polydispersity index less than 5. 16. The composition of claim 14, wherein the composition has a polydispersity index less than 2. 17. The composition of claim 14, wherein the composition has a polydispersity index less than 1.5. 18. The composition of claim 14, wherein the individual repeating subunits of said glycosaminoglycan mimetics bind to growth factors, neurotrophins, axon guidance proteins, inflammatory proteins, myelin associated proteins or their corresponding cell surface receptors. 19. The composition of claim 14, wherein the composition inhibits neural growth with an EC50 of 1 uM or less when assayed in an in vitro assay. 20. The composition of claim 19, wherein the EC50 is 25 nM or less. 21. The composition of claim 19, wherein the EC50 is 5 nM or less. 22. The composition of claim 14, wherein the composition stimulates neural growth with an EC50 of 1 uM or less when assayed in an in vitro assay. 23. The composition of claim 22, wherein the EC50 is 25 nM or less. 24. The composition of claim 22, wherein the EC50 is 5 nM or less. 25. A kit comprising a container containing a composition of claim 14; and instructions for use of said composition for inhibiting or stimulating neural growth. 26. A composition comprising a homogeneous population of the polymer of claim 1. 27. A method for obtaining a therapeutic benefit for an injury or disorder in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of the polymer of claim 1, wherein the injury or disorder is selected from the group consisting of Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, amyotrophic lateral sclerosis, multiple sclerosis, spinal cord injury, neuronal injury, stroke, peripheral neuropathy, osteoarthritis, pulmonary embolism, and deep vein thrombosis. 28. A method for screening for glycomimetic stimulators or inhibitors of neural growth, wherein the method comprises: contacting cultured neurons with the polymer of claim 1, and determining an effect on neural growth in axon length relative to a control. 29. A method of modulating neural growth in a neural cell, wherein the method comprises administering an effective amount of the polymer of claim 1, wherein said neural cell is a brain cell, a stem cell, a central nervous system (CNS) cell, or a peripheral neural cell. 30. The method of claim 29, wherein the polymer promotes regeneration of an injured or severed nerve or nerve tissue or promotes outgrowth in said neural cell. 31. The method of claim 29, wherein the polymer promotes neural cell growth in a cultured neuron. 32. The method of claim 31, wherein the cultured neuron is a hippocampal neuron, dopaminergic neuron, dorsal root ganglion neuron, motor neuron, or sensory neuron.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (14)
Vila Pahi, Francisco Javier; Flores Salgado, Francesc; Ruhi Roura, Ramon; Arnau Pastor, Narcis, Disaccharides with anti-arthrosic properties.
Kiessling Laura L. (2320 Lakeland Ave. Madison WI 53704) Manning David D. (1906 Pike Dr. ; Apt. 1 Madison WI 53713) Mortell Kathleen H. (202 G Eagle Heights Madison WI 53705), Polyglycomers.
Clark Steven C. (Winchester MA) Ciarletta Agnes B. (Tewksbury MA) Yang Yu-Chung (Arlington MA), Primate hematopoietic growth factors IL-3 and pharmaceutical compositions.
Axel Richard (New York NY) Wigler Michael H. (Cold Spring Harbor NY) Silverstein Saul J. (Irvington NY), Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials.
D'Agostino, Jeffrey A.; Carter, Andrew J.; Watterson, Arthur; Lane, Joseph P., Method and apparatus for treating bone fractures, and/or for fortifying and/or augmenting bone, including the provision and use of composite implants.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.