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. 2023 Oct 19;28(20):7165. doi: 10.3390/molecules28207165

Table 1.

Similarities and differences between LPPS and SPPS. Parameters taken into account for comparison of the two techniques are report in bold in the first column on the left.

Liquid-Phase Peptide Synthesis (LPPS) Solid-Phase Peptide Synthesis (SPPS)
Medium Solution Insoluble polymer
Batch size Any (usually large scale) Any (usually small scale)
Timing Slow Fast
Automation Difficult Semi- or fully-automated
Synthetic strategy Generally convergent Stepwise
Protecting groups employed Typically Boc or Z Typically Fmoc
Side-chain protection Minimum Maximum
Consumption of AA Moderate High
In-process analysis Direct monitoring (e.g., HPLC) Indirect monitoring
Purification of intermediates Possible (usually by precipitation) Not possible
Final purification Relatively simple Laborious