Solid phase peptide synthesis of a Gramicidin A analogue with high aqueous solubility that can generate native GA upon exposure to physiological pH
(English)In: International Journal of Peptide Research and Therapeutics, ISSN 1573-3904Article in journal (Refereed) Submitted
Gramicidin A (GA) was synthesized by anchoring Fmoc-ethanolamine to a 2-chlorotrityl resin and the peptide chain was assembled using COMU activated Fmoc amino acid followed by introduction of formyl-valine at the N-terminus. In contrast to other synthesis of GA reported in the literature, all four tryptophan residues were coupled as the recently described derivative Fmoc-Trp(Boc-Sar-Sar)-OH. The peptide was cleaved from the resin with TFA containing 1 % anisole simultaneously with the Boc groups resulting in the GA derivate; (H-Sar-Sar-)4-GA, in which all four indole nitrogens are modified by the protonated H-Sar-Sar- dipeptidyl moiety. Compared to native GA this derivative had an at least 10 000 fold higher solubility in water. Upon exposure to physiological pH, the H-Sar-Sar- groups were cleaved by an intramolecular cyclization reaction producing native GA although experimental limitations related to the solubilites of the peptide prevented us from demonstrate complete conversion of (H-Sar-Sar-)4-GA to native GA.
Research subject Neurochemistry with Molecular Neurobiology
IdentifiersURN: urn:nbn:se:su:diva-72969OAI: oai:DiVA.org:su-72969DiVA: diva2:504649