29133-55-9Relevant articles and documents
Thyrotropin-releasing hormone loaded and chitosan engineered polymeric nanoparticles: Towards effective delivery of neuropeptides
Kaur, Sarabjit,Bhararia, Avani,Sharma, Krishna K.,Mittal, Sherry,Jain, Rahul,Wangoo, Nishima,Sharma, Rohit K.
, p. 5324 - 5332 (2016/06/09)
Thyrotropin-Releasing Hormone (TRH), a tripeptide amide with molecular formula L-pGlu-L-His-L-Pro-NH2, is used in the treatment of brain/spinal injury and certain central nervous system (CNS) disorders, including schizophrenia, Alzheimer's disease, epilepsy, depression, shock and ischemia due to its profound effects on the CNS. However, TRH's therapeutic activity is severely hampered because of instability and hydrophilicity owing to its peptidic nature which results into ineffective penetration into the blood brain barrier. In the present study, we report the synthesis and stability studies of novel chitosan engineered TRH encapsulated poly(lactide-co-glycolide) (PLGA) based nanoformulation. The aim of such an encapsulation is to allow effective delivery of TRH in biological systems as the peptidase degrade naked TRH. The synthesis of TRH was carried out manually in solution phase followed by its encapsulation using PLGA to form polymeric nanoparticles (NPs) via nanoprecipitation technique. Different parameters such as type of organic phase, concentration of stabilizer, ratio of organic phase and aqueous phase, rate of addition of organic phase were optimized, tested and evaluated for particle size, encapsulation efficiency, and stability of NPs. The TRH-PLGA NPs were then surface modified with chitosan to achieve positive surface charge rendering them potential membrane penetrating agents. PLGA, PLGA-TRH, Chitosan-PLGA and Chitosan-PLGA-TRH NPs were characterized and analyzed using Dynamic Light Scattering (DLS), Transmissiom Electron Microscopy (TEM) and Infra-red spectroscopic techniques.
Further Studies on the Protection of Histidine Side Chains in Peptide Synthesis: The Use of the ?-Benzyloxymethyl Group
Brown, Tom,Jones, John H.,Richards, John D.
, p. 1553 - 1562 (2007/10/02)
Further studies on the use in peptide synthesis of N(?)-phenacyl protection for histidine side chains have shown that whilst this prevents the side chain-induced racemization which can occur if there is a lone pair of electrons available at the ?-nitrogen, there are concomitant drawbacks.As an alternative approach to the racemisation problem, the effect of halogenation of the heterocyclic ring carbons (to diminish the availability of the ?-nitrogen lone pair) has been investigated.This gives derivatives which are convenient in both classical and solid-phase applications, the halogen modifying groups being removed at the last stage by catalytic hydrogenolysis over a rhodium catalyst.Racemization is suppressed as expected, but it is not eleminated completely: direct blockade of the ?-nitrogen appears to be indispensable for its complete prohibition.Protection of the ?-nitrogen with a benzyloxymethyl group has now been found to be much more satisfactory than the use of the phenacyl group for this purpose.A ?-benzyloxymethyl substituent not only prohibits side chain-induced racemisation but also gives derivatives with convenient physical properties which can be incorporated into well estblished classical and solid-phase strategies without the need for any novel or additional operations or changes in protocol.The protecting group is stable to basic conditions, to trifluoroacetic acid, and to aqueous solutions of carboxylic acids, but is cleaved cleanly and rapidly by hydrogen bromide in trifluoroacetic acid or by catalytic hydrogenolysis.N(α)-t-Butoxycarbonyl-N(?)-benzyloxymethyl-L-histidine has been prepared in good yield by a simple procedure from an easily accessible intermediate and isolated as a crystalline solid; its use has been demonstrated by a number of exercises including a solid-phase synthesis of 5-isoleucine-angiotensin II and a classical synthesis of trihistidine.
