ABSTRACT
Acquired Immune Deficiency Syndrome [AIDS] is a disease infection mix, which is primarily because of 'deficient' immune system. Human Immune-deficiency Virus [HIV] makes the immune system susceptible to many infections by infiltrating it. Many researchers believe that HIV is a mutated form of Simian Immune-deficiency Virus [SIV]. After being clinically discovered in 1981 in America, it is said to have caused 36 million deaths. Treatment of AIDS has been a 'burning ' issue ever since its discovery. There is no cure for AIDS! Although, Recombinant Transcriptase Inhibitors [RTis] are being considered a major treatment against HIV that can not only lessen the effect of HIV but also can prolong the life of HIV positive patients. More recent advancement includes 'transplantation of transgenic stem cells' in HIV positive patients. As latency of HIV provirus in host genome is the preeminent weapon of this virus against RTis that compel it to hide from host immune system and a persistent pathogen thereof. Thus, epigenetic activation of latent provirus pool by methyl inhibitors along with nontoxic chemical drugs seems to be a more promising treatment to avoid the burden of lifelong RTI
ABSTRACT
Di-branched [Y-shaped] polyethylene glycols [PEGs] are considered more effective than linear molecules to enhance the efficacy of the conjugated drug. In the present study interferon alpha-2a was conjugated with three different 40 KDa di-branched PEGs. The results of this study show that length and/or the structure of linker between PEG and the protein is also involved in the synthesis, in vitro biological activity and stability of the conjugate. Three conjugates i.e., mPEG2L-IFN, mPEG2P-IFN and mPEG2M-IFN yielded 25%, 24% and 17%, with bioactivities 2.8 x 10[6] IU/mg, 3.95 x 10[6] IU/mg and 6.7 x 10[6] IU/mg, respectively. The order of bioactivity stability is mPEG[2]L-IFN > mPEG[2]P-IFN > mPEG[2]M-IFN > IFN [native]. We report that although lengthy linkers are more reactive in terms of conjugation, they have opposite effect on the in vitro bioactivity of the conjugate. PEGylation as a whole increases the stability of the conjugate, and linkers also add in stability