Solid-phase peptide synthesis (SPPS), C-terminal vs. side-chain anchoring: a reality or a myth

• Published in: Amino acids Vol. 46; no. 8; pp. 1827 - 1838
• Main Authors: Cherkupally, Prabhakar, Acosta, Gerardo A., Ramesh, Suhas, De la Torre, Beatriz G., Govender, Thavendran, Kruger, Hendrik G., Albericio, Fernando
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.08.2014; Springer Nature B.V
• Subjects: Amino Acid Sequence; Amino acids; Analytical Chemistry; Anchoring; Anchors; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Chromatography, High Pressure Liquid; Life Sciences; Minireview Article; Molecular Structure; Neurobiology; Peptide synthesis; Peptides; Peptides - chemical synthesis; Polymers; Proteomics; resins; Side reactions; Solid phase methods; Solid phase synthesis; Solid-Phase Synthesis Techniques - methods; Stability; Strategy; Synthesis; Stepwise elongation; Side-chain anchoring; Solid-phase peptide synthesis; C-terminal acid peptide
• ISSN: 0939-4451; 1438-2199; 1438-2199
• DOI: 10.1007/s00726-014-1746-7

Here we review the strategies for the solid-phase synthesis of peptides starting from the side chain of the C-terminal amino acid. Furthermore, we provide experimental data to support that C-terminal and side-chain syntheses give similar results in terms of purity. However, the stability of the two bonds that anchor the peptide to the polymer may determine the overall yield and this should be considered for the large-scale production of peptides. In addition, resins/linkers which do not subject to side reactions can be preferred for some peptides.