In designing the chemical synthesis of 2N4R Tau, we were mindful of the recent developments in preparative protein methodologies which have been extensively discussed elsewhere. Several critical methods were employed to facilitate successful Solid Phase Peptide Synthesis (SPPS) of Tau segments. One of the key strategies involved the preparation of synthetic peptides that contained fewer than 50 amino acids, facilitating a more manageable purification process. Thioester synthesis needed for the successful Native Chemical Ligation (NCL) also played a pivotal role in our synthesis. We incorporated a technique originally developed by Dawson, which entailed the use