title: Synthesis and sequential deprotection of triblock copolypept(o)ides using orthogonal protective group chemistry.
abstract: The synthesis of triblock copolymers based on polysarcosine, poly-N-ε-t-butyloxycarbonyl-l-lysine, and poly-N-ε-t-trifluoroacetyl-l-lysine by ring-opening polymerization of the corresponding α-amino acid N-carboxyanhydrides (NCAs) is described. For the synthesis of N-ε-t-butyloxycarbonyl-l-lysine (lysine(Boc)) NCAs, an acid-free method using trimethylsilylchloride/triethylamine as hydrochloric acid (HCl) scavengers is presented. This approach enables the synthesis of lysine(Boc) NCA of high purity (melting point 138.3 °C) in high yields. For triblock copolypept(o)ides, the degree of polymerization (Xn ) of the polysarcosine block is varied between 200 and 600; poly-N-ε-t-butyloxycarbonyl-l-lysine and poly-N-ε-t-trifluoroacetyl-l-lysine blocks are designed to have a Xn in the range of 10-50. The polypeptide-polypeptoid hybrids (polypept(o)ides) can be synthesized with precise control of molecular weight, high end group integrity, and dispersities indices between 1.1 and 1.2. But more important, the use of tert-butyloxycarbonyl- and trifluoroacetyl-protecting groups allows the selective, orthogonal deprotection of both blocks, which enables further postpolymerization modification reactions in a block-selective manner. Therefore, the presented synthetic approach provides a versatile pathway to triblock copolypept(o)ides, in which functionalities can be separated in specific blocks.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099, Mainz, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Heller
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weber
authors.forename: Alexander
authors.initials: A
authors.lastname: Birke
authors.forename: Matthias
authors.initials: M
authors.lastname: Barz
mesh_terms: D010455:Peptides / Q000138:chemical synthesis*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D058105:Polymerization; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
chemical_list: D010455:Peptides; D011107:Polylysine; C015475:polysarcosine; D012521:Sarcosine
keywords: orthogonal deprotection; polypeptides; polysarcosines; triblock copolymers