Native Chemical Ligation: Ultrafast Synthesis of Block Copolymers

Abstract

Native chemical ligation (NCL) allows the chemical synthesis of proteins and peptides with excellent efficiency, starting from a mixture of unprotected short peptide fragments. The chemo-and regioselectivity of NCL provide access to functional biomacromolecules such as peptides without protection−deprotection strategies under mild conditions. In contrast, less progress has been made in non-natural polymer conjugation. Metal contamination, synthetic difficulties, laborious purifications, or lack of functional group tolerance limits the complex functional polymer design. Here, we have studied the potential of NCL for non-natural polymer conjugation. Diblock and ABA triblock copolymers were synthesized via NCL with high efficiency within 1 h at room temperature. An A-alt-B block copolymer was also synthesized with a remarkable degree of polymerization from bifunctional thioester and cysteine end functional polymers. The size exclusion chromatography and NMR spectroscopy analyses of the synthesized polymers confirmed the block structure of the polymers and the excellent efficiency of NCL for non-natural polymer conjugation.

Chain transfer agents for the catalytic ring opening metathesis polymerization of norbornenes

“…Despite all this, there are limited literature reports regarding ligation between two synthetic polymers. 50 Inspired by the efficiency and speed of NCL to produce block copolymers, 51 here, we report an economical, atom-efficient way to make such polymers under very mild reaction conditions. Commercially available poly( l -lactide) (PLA, M n = 20 kDa, Đ = 1.08) was end-functionalized with cysteine using a protection and deprotection strategy (see ESI‡).…”

Orthogonal Covalent Entrapment of Cargo into Biodegradable Polymeric Micelles via Native Chemical Ligation

“…42 Recently, the ultrafast synthesis of block copolymers via NCL was also demonstrated. 43 Here, we designed a trifunctional cross-linker containing two cysteine residues and an azide functionality to employ NCL as a cross-linking strategy for the formation of CCPMs and simultaneous drug entrapment. The cysteine residues can react with thioglycolate modified copolymers via NCL while the azide functionality can be employed for (copper-free) click chemistry coupling of drugs or fluorescent dye conjugates.…”

“…Native chemical ligation (NCL), introduced by Kent and co-workers in 1994, is a mild bio-orthogonal reaction between a N -terminal cysteine residue and a thioester that readily proceeds under physiological conditions. , Previously, we have shown the use of NCL for the cross-linking of PMs by complementary reaction of two N -isopropylacrylamide based copolymers modified with either cysteine or thioglycolate residues . Recently, the ultrafast synthesis of block copolymers via NCL was also demonstrated …”

Catalytic living ROMP: block copolymers from macro-chain transfer agents

“…[1][2][3][4][5][6] The most common synthetic strategies are based on (i) sequential addition of monomers via a living polymerization technique, (ii) coupling reactions between different chain ends of polymers and (iii) polymerization from macroinitiators. [7][8][9][10][11][12][13][14] Although many living polymerization techniques are known that allow the preparation of multiblock copolymers with controlled molecular weight and dispersity, the same polymerization technique is used to create all blocks of the copolymer in most cases. 15,16 A second approach towards BCP synthesis includes the conjugation of suitably end-functionalized polymeric chains with one another.…”