Solid-Phase Synthesis of C-Terminus Cysteine Peptide Acids

• DOI: 10.1021/acs.oprd.2c00321
• Publication Date: 2022-11-15T18:22:53Z
• Authors: Sinenhlanhla N. M...; Amit Chakraborty; Ralph Schönleber; Fernando Albericio; Beatriz G. de la ...
• Keywords: Side chain; Epimer; Residue (chemistry); Peptide Synthesis; Solid-Phase Synthesis

Cysteine (Cys) is a key amino acid in many therapeutic peptides. For research and industrial purposes, solid-phase peptide synthesis the method of choice for preparation most The C-terminal Cys acids problematic because it accompanied by side reaction, namely, abstraction α-H from residue, which leads to formation three products: epimer two N-piperidinyl-Ala Here, we used chlorotrityl chloride resin conduct rational in-depth study this reaction. following variables were examined: removal fluorenylmethoxycarbonyl (Fmoc) group different bases, presence or absence an rectifier buffering base, thiol side-chain protection. In conclusion, use Fmoc-Cys protected with tetrahydropyran (Thp) 4-methoxytrityl (Mmt) along 30% 4-methylpiperidine 0.5 M OxymaPure-DMF Fmoc assures minimization as demonstrated model confirmed elongation somatostatin.