Synthesis, Table of Contents CC BY-ND-NC 4.0 · Synthesis 2019; 51(01): 31-39DOI: 10.1055/s-0037-1610202 paper Copyright with the author Syntheses of Cyanophycin Segments for Investigations of Cell-Penetration Marcel Grogg Laboratorium für Organische Chemie (LOC), Departement Chemie und Angewandte, Biowissenschaften (D-CHAB), ETH-Zürich, Hönggerberg HCI, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland Email: seebach@org.chem.ethz.ch , Donald Hilvert Laboratorium für Organische Chemie (LOC), Departement Chemie und Angewandte, Biowissenschaften (D-CHAB), ETH-Zürich, Hönggerberg HCI, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland Email: seebach@org.chem.ethz.ch , Albert K. Beck Laboratorium für Organische Chemie (LOC), Departement Chemie und Angewandte, Biowissenschaften (D-CHAB), ETH-Zürich, Hönggerberg HCI, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland Email: seebach@org.chem.ethz.ch , Dieter Seebach* Laboratorium für Organische Chemie (LOC), Departement Chemie und Angewandte, Biowissenschaften (D-CHAB), ETH-Zürich, Hönggerberg HCI, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland Email: seebach@org.chem.ethz.ch › Author Affiliations Recommend Article Abstract All articles of this category § This author did all the experiments Abstract Novel guanidinium-rich oligopeptide derivatives R-[Adp(X)]8-NH2 are described, which consist of an octa-aspartic acid backbone with argininylated side chains that are derived from the biopolymer cyanophycin [H-(Adp)n-OH]. The Fmoc-Adp(X,Pbf)-OH building blocks for solid-state peptide synthesis (SSPS) of Adp octamers were prepared from Fmoc-Arg(Pbf)-OH and Fmoc-Asp-OAll. Coupling on PAL resin provided four octamers with and without N-terminal fluorescent groups (FAM) and C-terminal amide groups. Milligram quantities of Adp-octamers were isolated after preparative HPLC purification. The structure of the novel guanidinium-rich oligomers is unique insofar as the side chains of the Asp8-backbone include both a guanidino and a carboxylic acid group, the influence of which will be tested with the corresponding ester and amide derivatives that were synthesized in parallel. Unusual cell-penetrating properties of the Adp-octamers are expected. Key words Key wordsguanidinium-rich oligopeptides - β3/α-Asp-Arg-dipeptide building block - biopolymer cyanophycin - solid-state peptide synthesis - cell-penetrating peptides Full Text References References 1 Frankel AD. Pabo CO. Cell 1988; 55: 1189 2 Derossi AH. Joliot AH. Chassaing G. Prochiantz A. J. Biol. Chem. 1994; 269: 10444 3a Wender PA. Mitchell DJ. Pattabiraman K. Pelkey ET. Steinman L. Rothbard JB. Proc. Natl. Acad. Sci. U S A 2000; 97: 13003 3b Geihe Stanzl E. Trantow BM. Vargas JR. Wender PA. Acc. Chem. Res. 2013; 46: 2944 4a Futaki S. Suzuki T. Ohashi W. Yagami T. Tanaka S. Ueda K. Sugiura Y. J. Biol. Chem. 2001; 276: 5836 4b Futaki S. Nakase I. Acc. Chem. Res. 2017; 50: 2449 5 Copolovici DM. Langel K. Eriste E. Langel Ü. ACS Nano 2014; 8: 1972 6 Grogg M.; Hilvert D.; Ebert M.-O.; Beck A. K.; Seebach D.; Kurth F.; Dittrich P. S.; Sparr C.; Wittlin S.; Rottmann M.; Mäser P. Helv. Chim. Acta 2018, 15, DOI: 10.1002/hlca.201800112. 7 Simon RD. Proc. Natl. Acad. Sci. U S A 1971; 68: 265 8 Frommeyer M. Wiefel L. Steinbüchel A. Crit. Rev. Biotechnol. 2016; 36: 153; and references cited therein 9a Sallam A. Kast A. Przybilla S. Meiswinkel T. Steinbüchel A. Appl. Environ. Microbiol. 2009; 75: 29 ; and earlier references cited therein 9b Krehenbrink M. Sallam A. Steinbüchel A. Biotechnical Approaches to Dipeptide Production . In Industrial Biocatalysis . Grunwald P. Pan Stanford Publishing Pte. Ltd; Singapore: 2015. Chap. 2 ; and earlier references cited therein 10 Seebach D. Beck AK. Bierbaum DJ. Chem. Biodiv. 2004; 1: 1111 11 Kolesinska B. Wasko J. Kaminski Z. Geueke B. Kohler H.-PE. Seebach D. Helv. Chim. Acta 2018; 101: e1700259 12 Heck T. Limbach M. Geueke B. Zachariasc M. Gardiner J. Kohler H.-PE. Seebach D. Chem. Biodiv. 2006; 3: 1325 13 Albericio F. Barany G. Int. J. Pept. Protein Res. 1987; 30: 206 14 Kurth F.; Dittrich P. S.; Walde P. J.; Seebach D. Chem. Biodiv. 2018, DOI: 10.1002/cbdv.201800302.
