As mentioned earlier, in the past decades, the development of SPPS has involved a long series of improvements upon existing methodologies. For this purpose, a vast number of resin and linkers have been developed and optimized, enabling a wide range of application. The resin determines the physical properties, e.g., swelling which is necessary for diffusion and accessibility of active sites. It is also required to be chemically and mechanically stable, to allow an appropriate and convenient loading of the substrates, to be permeable to solvents and reactants, moreover to have a homogeneous bead size.

While the linker determines the conditions that can be used throughout peptide chain assembly, and also the nature of the C-terminal functionality possessing C-terminal carboxylic acids or primary amides. Although resins and likers are separate entities, it cannot be overemphasized that in all but a few cases, the linkage and resin selections are independent of one another; and frequently, a successful SPPS depends upon the choice of these.   For the sake of generality, the description below will focus substantially on Fmoc-based chemistry, since this master thesis utilizes Fmoc-strategy.  In consideration of the foregoing, selecting the proper insoluble polymer support (resin) is often the first requirement during solid-phase peptide synthesis. The decision regarding this depends on whether the plan is to perform Fmoc-based automated SPPS under continuous-flow mode or batch-wise SPPS using Fmoc-based chemistry. Over the years, the polymeric supports for solid-phase synthesis have matured considerably, and a limited number of resins such as, polystyrene (PS), PS-functionalized polyethylene glycol (PEG), as well as pure cross-linked PEG resins have been developed and become commercially available. At present, these are classes of resins that are most commonly used during solid-phase peptide synthesis.

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 Conventional polystyrene is a highly hydrophobic polymer cross-linked with 1% of divinylbenzen (DVB), and was the first solid polymer support to be introduced and used by Merrifeild in the 1960s. This type of swelling polymer is still widely used today and is the most appropriate support to be used for automated/manual batch-wise solid-phase synthesis of short- to medium-length peptides. A PS resin possesses qualities including free flowing, powder like consistency when dry, facile swelling in most organic solvents, mechanical stability throughout repetitive vortexing, stirring, ability to assist in the diffusion of reactants during coupling and/or washing, and not to mention inexpensive and widely available. PS-DVB resins swell immediately in contact with nonpolar aprotic solvents (e.

g. DCM),