Kim Hoang Yen Duong1, Viktória Goldschmidt Gőz2, István Pintér1, András Perczel3,4. 1. Laboratory of Structural Chemistry and Biology, Institute of Chemistry, ELTE Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary. 2. MTA-ELTE Protein Modeling Research Group, ELTE Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary. 3. Laboratory of Structural Chemistry and Biology, Institute of Chemistry, ELTE Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary. perczel.andras@ttk.elte.hu. 4. MTA-ELTE Protein Modeling Research Group, ELTE Eötvös Loránd University, Pázmány P. stny. 1/A, Budapest, 1117, Hungary. perczel.andras@ttk.elte.hu.
Abstract
Complementary to hydrophobic five membered ring β-amino acids (e.g. ACPC), β-sugar amino acids (β-SAAs) have found increasing application as hydrophilic building blocks of foldamers and α/β chimeric peptides. Fmoc-protected β-SAAs [e.g. Fmoc-RibAFU(ip)-OH] are indeed useful Lego elements, ready to use for SPPS. The removal of 1,2-OH isopropylidene protecting group increasing the hydrophilicity of such SAA is presented here. We first used N3-RibAFU(ip)-OH model compound to optimize mild deprotection conditions. The formation of the 1,2-OH free product N3-RibAFU-OH and its methyl glycoside methyl ester, N3-RibAFU(Me)-OMe were monitored by RP-HPLC and found that either 50% TFA or 8 eqv. Amberlite IR-120 H+ resin in MeOH are optimal reagents for the effective deprotection. These conditions were then successfully applied for the synthesis of chimeric oligopeptide: -GG-X-GG- [X=RibAFU(ip)]. We found the established conditions to be effective and-at the same time-sufficiently mild to remove 1,2-O-isopropylidene protection and thus, it is proposed to be used in the synthesis of oligo- and polypeptides of complex sequence combination.
Complementary to hydrophobic five membered ring β-amino acids (e.g. anclass="Chemical">ACPC), β-class="Gene">an class="Chemical">sugar amino acids (β-SAAs) have found increasing application as hydrophilic building blocks of foldamers and α/β chimeric peptides. Fmoc-protected β-SAAs [e.g. Fmoc-RibAFU(ip)-OH] are indeed useful Lego elements, ready to use for SPPS. The removal of 1,2-OH isopropylidene protecting group increasing the hydrophilicity of such SAA is presented here. We first used N3-RibAFU(ip)-OH model compound to optimize mild deprotection conditions. The formation of the 1,2-OH free product N3-RibAFU-OH and its methyl glycoside methyl ester, N3-RibAFU(Me)-OMe were monitored by RP-HPLC and found that either 50% TFA or 8 eqv. Amberlite IR-120 H+ resin in MeOH are optimal reagents for the effective deprotection. These conditions were then successfully applied for the synthesis of chimeric oligopeptide: -GG-X-GG- [X=RibAFU(ip)]. We found the established conditions to be effective and-at the same time-sufficiently mild to remove 1,2-O-isopropylidene protection and thus, it is proposed to be used in the synthesis of oligo- and polypeptides of complex sequence combination.
Authors: Joana T Ferreira; João Pina; Carlos A F Ribeiro; Rosa Fernandes; João P C Tomé; M Salomé Rodríguez-Morgade; Tomás Torres Journal: Chemistry Date: 2019-11-07 Impact factor: 5.236