Pep­tide syn­the­sis occurs by cou­pling of the amine or NH2 group of one amino acid to the ter­mi­nal car­boxyl or COOH group of the anoth­er amino acid. The blog dis­cuss­es impor­tant facts about sol­id phase pep­tide synthesis.

Sol­id phase pep­tide syn­the­sis or SPPS was pio­neered by Bruce Mer­ri­field in 1963 that brought about a rev­o­lu­tion in the pro­tein syn­the­sis indus­try. The process has proven to be a major tool for the cre­ation of nat­ur­al or organ­ic pep­tides. Pep­tide syn­the­sis on a sol­id sup­port facil­i­tates sep­a­ra­tion from sol­u­ble reagents and wash­ing steps. Com­posed of amino acids, pep­tides are chem­i­cal­ly linked togeth­er through a pep­tide bond. Chemical bonding

The sol­id phase pep­tide syn­the­sis (SPPS)

Dur­ing the process, small beads, on which pep­tide chains are to be built, are treat­ed with link­ers. The beads retain their bond with pep­tides until they are cleaved by a chem­i­cal reagent, such as tri­flouroacetic acid. A syn­the­sis envi­ron­ment is cre­at­ed by these beads in which the pep­tide chains that are being cre­at­ed are retained on the fil­ter mate­r­i­al, where­as the reagents used to cre­ate them pass through. The two most com­mon­ly used forms of sol­id phase pep­tide syn­the­sis are Boc and Fmoc. Con­trary to ribo­some pro­tein syn­the­sis, sol­id phase pep­tide syn­the­sis takes place on a C-ter­mi­­nal to N-ter­mi­­nal. The N-Ter­mi­­nal of amino acid monomer is pro­tect­ed by two groups and added on to an unpro­tect­ed amino acid chain. Although, a num­ber of research groups still per­form the process man­u­al­ly, auto­mat­ed tech­niques have also been invent­ed.

SPPS – The Steps Involved

The main steps involved in the process include : 
  • De-pro­tec­­tion – The process aims to remove the Fmoc group from the N-ter­mi­nus of the grow­ing pep­tide chain and allows the next amino acid to be coupled.
  • Wash – The resin that con­tains the pep­tide is washed with sol­vent thor­ough­ly a cou­ple of times to clean the resin before the cou­pling reac­tion could begin.
  • Cou­pling – An amino acid is added to the pep­tide chain. Acti­va­tion of the amino acid is required for this process before it can be linked to the grow­ing pep­tide chain.
  • Wash – The resin is washed again with sol­vent to clean it com­plete­ly before begin­ning the next cycle.

These steps are repeat­ed until the desired pep­tide sequences are assem­bled on the resin. The last step involves cleav­age of the pep­tide from the resin.

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