- DIPEPTIDE MIMETICS OF NGF AND BDNF NEUROTROPHINS
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The invention relates to compounds having either agonist or antagonist activities for the neurotrophins NGF and BDNF and represented by monomeric or dimeric substituted dipeptides that are analogs of the exposed portions of loop 1 or loop 4 regions of these neurotrophins near or at a beta-turn of the respective loop. N-acylated substituents of these dipeptides are biostereoisomers of the amino acid residues preceding these dipeptide sequences in the neurotrophin primary structure. The dimeric structure is produced advantageously by using hexatnethylenediaanine to which dipeptides are attached via their carboxyl groups. The claimed compounds displayed neuroprotective and differentiation-inducing activities in cellular models and enhanced the amount of phosphorylated tyrosine kinase A and the heat shock proteins Hsp32 and Hsp70 in the concentration range of 10 -9 to 10 -5 M. They also displayed neuroprotective, anti-parkinsonian, anti-stroke, anti-ischemic, anti-depressant and anti-amnestic activities in animal models and were active in experimental models of Alzheimer's disease. These in vivo effects of the claimed compounds are displayed in the dose range of 0.01 to 10 mg/kg when administered intraperitoneally.
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Paragraph 0055
(2019/04/16)
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- Solution-phase synthesis of a muramyl dipeptide analogue MDA
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The solution-phase synthesis of a muramyl dipeptide (MDP) analogue of Nα-[4-chlorocinnamoyl-l-alanyl-d-isoglutaminyl]-l-lysine (MDA, 2) is reported that possesses the features of easy feasibility, safety and low cost in large scale of synthesis.
- Zhao, Nan,Ma, Yao,Liu, Gang
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p. 1443 - 1446
(2012/06/04)
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- Synthesis of biologically active biotinylated muramyl dipeptides
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Muramyl dipeptide (MDP) is believed to interact with an innate immune receptor, Nod2. To identify the cellular receptor for MDP, we have synthesized biotinylated MDP isomers and tested the ability of these compounds to activate Nod2 in a cell-based assay. We found that the modification of MDP does not perturb its ability to activate Nod2. These tagged versions of MDP will be useful to identify the cellular receptor of the immunostimulatory molecules.
- Grimes, Catherine Leimkuhler,Podolsky, Daniel K.,O'Shea, Erin K.
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supporting information; experimental part
p. 6061 - 6063
(2010/11/17)
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- Conformationally flexible platelet aggregation inhibitors based on the tetrapeptide Arg-Gly-Asp-Arg
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A series of nonpeptide fibrinogen receptor antagonists based upon the tetrapeptide Arg-Gly-Asp-Arg were prepared. These relatively simple derivatives incorporate a high degree of conformational flexibility that was anticipated to allow them to attain the
- Klein,Czekaj,Molino,Chu
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p. 833 - 839
(2007/10/03)
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- Synthesis of some conformationally constrained analogues of muramyl dipeptide (MDP)
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Synthesis of three conformationally constrained analogues of MDP, viz AcMur-Δ-Ala-D-isoGln (1), AcMur-Aib-D-isoGln (2) and AcnorMur-Aib-D-isoGln (3) is described. Coupling of the protected carbohydrate derivatives with appropriate dipeptide amines in the
- Kundu,Rizvi,Srivastava,Haq,Mathur
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p. 409 - 413
(2007/10/02)
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- Structure-Activity Studies on the C-Terminal Hexapeptide of Substance P with Modifications at the Glutaminyl and Methioninyl Residues
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Analogues of 6>-SP6-11 have been synthesized in which the SCH3 group of the Met11 side chain is replaced by other functional groups, such as (CH2)2NH2, COOH, CONH2, and COOR, which have basic, acidic, or neutral charac
- Poulos, Constantine,Stavropoulos, George,Brown, John R.,Jordan, Christopher C.
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p. 1512 - 1515
(2007/10/02)
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- SYNTHESIS AND FAST-ATOM-BOMBARDMENT-MASS SPECTROMETRY OF N-ACETYLMURAMOYL-L-ALANYL-D-ISOGLUTAMINE (MDP)
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N-Acetylmuramoyl-L-alanyl-D-isoglutamine (MDP) was synthesized by a series of condensation of appropriate reagents, followed by hydrogenolysis.Each intermediate step resulted in a stable, crystalline product.D-Isoglutamine 4-benzyl ester was condensed with N-(tert-butoxycarbonyl)-L-alanine N-hydroxysuccinimide ester, to give N-(tert-butoxycarbonyl)-L-alanyl-D-isoglutamine benzyl ester.Condensation of L-alanyl-D-isoglutamine benzyl ester with N-acetyl-1-O-benzyl-4,6-O-benzylidenemuramic acid, followed by hydrogenolysis, gave MDP.The synthetic scheme was shown to be capable of producing gram quantities of highly pure MDP, as well as a few of its analogs.The synthetic MDP was characterized by analytical and biological methods, and it was found that the use of fast-atom-bombardment-mass spectrometry may greatly simplify the characterization process.
- Phillips, Lawrence R.,Nishimura, Osamu,Fraser, Blair A.
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p. 275 - 286
(2007/10/02)
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