Discuss the Potential Problems such as Decreased cell permeability and Lack of polyglutamation.

• Write an in-depth review articles on METHOTREXATE specifically focused on treatment of Rheumatoid Arthritis, discuss the history, Drug mechanism and the strong “views”, current ongoing research of both the drug and disease. Further talk about the side effects of METHOTREXATE and propose a way to reduce the side effect.
• This is my proposal: to use homing peptide (NQR peptide: CLDNQRPKC)(look at the reference number 5 on the bottom of this page:Yang et al., 2011) and Synthesis of METHOTREXATE -Peptide Conjugate. The METHOTREXATE can possible could coupled to N-terminus of peptide by Peptide assembled on a resin (Syro peptide synthesizer, MTX-Peptide complex cleaved from solid using trifluoroacetic acid, Purified using HPLC, Confirmed using mass spectrometry). This proposal has to be the main point of the paper. Also, offer other possible synthesis options and/or techniques.
• Discuss the Potential Problems such as Decreased cell permeability and Lack of polyglutamation
• Compare this application with one of the current biologic treatment option of Rheumatoid Arthritis and try to prove that this has the upper hands.

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