Dendritic−Graft Polypeptides

Abstract

A new synthetic strategy for the preparation of highly branched, or dendritic−graft, polypeptides is presented. The synthetic strategy is based on a repetitive sequence of ring-opening copolymerization and deprotection steps. Comonomers for the ring-opening polymerization are a set of orthogonally protected l-lysine N-carboxyanhydride derivatives. After each polymerization step, selective removal of the ε-NH2 protecting groups of one of the monomers generates a number of new initiator sites that allow grafting of a successive generation of polypeptide branches. Following this strategy, dendritic−graft polypeptides containing up to ∼160 α-amino acids, corresponding to a number-average molecular weight of ∼40 kDa, could be obtained after only four ring-opening polymerization−deprotection cycles. In contrast to perfect dendrimers, the dendritic−graft polypeptides are neither structurally uniform nor monodisperse. Dendritic−graft polypeptides, however, are conveniently prepared in multigram quantities and do not require laborious purification procedures.

Polypeptide und 100 Jahre Chemie der α‐Aminosäure‐N‐carboxyanhydride

“…Dieselbe Arbeitsgruppe beschrieb auch eine alternative Synthesestrategie. [195] N e -Boc-oder N e -TFA-l-Lys-NCA wurden auf die freien N e -Aminogruppen der Poly(l-Lys)-Seitenketten gepfropt, dann wurden die Schutzgruppen von den Poly(l-Lys)-Seitenketten entfernt und die freigesetzten e-Aminogruppen wieder zum Aufpfropfen neuer Peptidketten genutzt.…”

Synthesis and Conformations of Dendronized Poly(l-lysine)

“…43 Briefly, poly(Z-L-lysine) was dissolved in TFA to make a 33 mg/mL solution, and a fourfold excess of HBr (33 % in acetic acid) relative to monomer units was added. The reaction was capped and stirred at rt for 4 h. The reaction mixture was then poured into diethyl ether to precipitate the product as the TFA salt, which was recovered by filtration and dried in vacuo to yield a pale yellow solid.…”

An Expeditious Multigram‐Scale Synthesis of Lysine Dendrigraft (DGL) Polymers by Aqueous N‐Carboxyanhydride Polycondensation

“…1 For clarity reasons, the term dendritic graft polyA C H T U N G T R E N N U N G (l-lysine), introduced by Klok et al, is only used in this paper when referring to the materials prepared according to their methods. [14,27] We selected the term dendrigraft and the abbreviation DGL (which denotes both dendrigraft poly-A C H T U N G T R E N N U N G (l-lysine) and l-lysine dendrigraft polymer) to refer to the new materials described in this report.…”

“…[13] Dendrigraft (also called dendritic graft or arborescent) polymers are the third, most recently discovered subset of dendritic polymers. Like dendrimers, their preparation in a generation-based scheme involves protective group manipulation combined with polymerisation steps, that is, either by cycles of protection, monomer polymerisation, and deprotection (so-called "grafting from" method), [14] or by using preformed polymers instead of molecular compounds as AB n building blocks in cycles of protection, condensation and deprotection (so-called "grafting onto" method). [3] Because they are no longer single-molecule compounds, dendrigraft polymers have a less controlled structure than dendrimers, but usually a much more regular architecture than hyperbranched polymers.…”

“…This dramatic molecular weight increase combined with the possibility of using relatively inexpensive monomers offers the potential to manufacture and develop dendrigraft polymers possessing dendrimer-like properties at a much lower cost. [15] As an example based on peptide bonds, Klok et al [14,16] reported the synthesis of dendritic graft polyA C H T U N G T R E N N U N G (l-lysine)s by iterative co-polycondensation of two differently N e -protected amino acid N-carboxyanhydrides (NCA) in dimethylformamide, followed by the selective removal of one of these sets of protecting groups; a final, complete deprotection step then afforded the desired dendritic graft polyA C H T U N G T R E N N U N G (llysine). [14] Our recent investigations on NCA chemistry in water (in connection with their possible key role in the emergence of life through the prebiotic chemistry of peptides), [17][18][19] gave us the opportunity to address the synthesis of lysine arborescent polymer in an original manner.…”