Polypeptide End-Capping Using Functionalized Isocyanates:  Preparation of Pentablock Copolymers

Abstract

The use of electrophiles (isocyanates, isothiocyanates, acid chlorides) to cap the N-terminal ends of polypeptides and the use of isocyanates to prepare poly(γ-benzyl-L-glutamate)-b-(nonpeptide polymer) block copolymers are described. This chemistry was also used to prepare poly(ethylene glycol)where polymer ) polyoctenamer, poly(ethylene glycol), or poly(dimethylsiloxane). These R,ω-diamino-terminated polymers (polymer) were used to prepare difunctional macroinitiators for the living polymerization of γ-benzyl-L-glutamic acid-N-carboxyanhydride (Glu NCA) to form triblock copolymers that were subsequently capped with isocyanate terminated poly(ethylene glycol) to give the pentablock copolymers. These methods allow the facile functionalization of the N-terminal ends of polypeptides from NCA polymerizations. They also were shown to allow the controlled preparation of "rod-coil" polypeptide-(nonpeptide polymer) multiblock architectures with good control over the chain lengths of the domains and without formation of homopolypeptide contaminants.

Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via Controlled NCA Polymerization

“…It is wellknown in NCA polymerizations that electrophiles, such as isocyanates, act as chain terminating agents by reaction with the propagating amine chain-ends [9]. Deming and coworkers reported that the reactive living nickelacycle polypeptide chain-ends could be quantitatively capped by reaction with excess isocyanate, isothiocyanate, or acid chloride [33]. Using this chemistry, they prepared isocyanate end-capped poly(ethylene glycol), PEG, and reacted this, in excess, with living poly(γ -benzyl-L-glutamate), PBLG, to obtain PBLG-b-PEG diblock copolymers (Eq.…”

Self‐assembly and responsiveness of polypeptide‐based block copolymers: How “Smart” behavior and topological complexity yield unique assembly in aqueous media

“…Similar strategies could be used to create this topology with a hydrophilic homopeptide, synthesized through ROP of NCAs, employing a small molecule diamine initiator as the center block and either a hydrophobic synthetic polymer/polypeptide as the outer blocks. In addition to the coupling chemistry used by Kiick, Deming et al 94 have used amine-isocyanate chemistries to proficiently create polypeptide multiblock hydrid polymers.…”

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

“…Im Falle der a-Aminosäure-NCAs gelang neben der Herstellung von Homopolypeptiden [99,100] die Synthese zahlreicher Diblock-, Triblock-und PentablockCopolypeptide. [101][102][103][104][105][106][107][108][109][110][111][112][113] Struktur und Eigenschaften dieser Blockcopolypeptide werden in Abschnitt 6 kommentiert.…”