Bioactive mesoglobules of poly(di(ethylene glycol) monomethyl ether methacrylate)–peptide conjugate

Abstract

This study describes the synthesis and aggregation behavior of thermosensitive poly(di(ethylene glycol) monomethyl ether methacrylate) (P(DEGMA‐ME)) conjugated with the fluorescently labeled pentapeptide glycine‐arginine‐lysine‐phenylalanine‐glycine‐dansyl (GRKFG‐Dns). The GRKFG‐Dns was obtained using Fmoc solid‐phase peptide synthesis and was modified with 2‐bromopropionic acid to initiate an atom transfer radical polymerization of di(ethylene glycol) monomethyl ether methacrylate (DEGMA‐ME). The polymerization led to a well‐defined P(DEGMA‐ME)–GRKFG‐Dns conjugate with a number average molar mass of 108,000 g/mol. The pentapeptide acted as a hydrophilic moiety that increased the phase transition temperature compared to the P(DEGMA‐ME) homopolymer of similar molar mass. The bioconjugate macromolecules aggregated in dilute aqueous solution into spherical particles (mesoglobules). The sizes of aggregates were easily controlled by changing the concentration and heating rate of the P(DEGMA‐ME)‐GRKFG‐Dns solution. The weight average molar masses and sizes of mesoglobules were determined based on light scattering measurements. Enzymatic hydrolysis of the bioconjugate in dilute solution was performed at temperatures below and above the cloud point temperature of the bioconjugate. The peptides were fully accessible to enzymatic digestion even when the macromolecules were aggregated to mesoglobules, indicating that the peptide segments in mesoglobules formed the external shell of the nanoparticles and could be easily released by enzymes. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

COMU: scope and limitations of the latest innovation in peptide acyl transfer reagents

“…Hence, COMU (16) has become a preferred peptide coupling reagent in many research groups. The possibility of using COMU (16) without excess base is an attractive methodology to reduce the degree of stereomutation in peptide couplings, which is a dramatic side reaction with severe implications in peptide purity and activity [3,18]. The optical purity of peptides synthesized by COMU (16) is much higher than HOBtanalogs in fragment couplings and even superior to HATU (5) in stepwise models [3].…”

Combined atom-transfer radical polymerization and ring-opening polymerization to design polymer-polypeptide copolymer conjugates toward self-aggregated hybrid micro/nanospheres for dye encapsulation

“…16,21,22 It is also known that ring-opening polymerization (ROP) of a-amino acid N-carboxyanhydride (NCA) initiated by nucleophiles or bases is the most common technique to synthesize different polypeptides. 23,24 In general, polymer-peptide/polypeptide conjugates are synthesized by "grafting from" technique instead of "grafting to" involving the following two protocols: (1) it is the preparation of the sequence-defined peptide segment by solid/solution-phase route followed by its transformation into macroinitiators for ATRP of various vinyl monomers to synthesize desired peptide-polymer conjuagtes, [25][26][27] (2) it is the synthesis of amino acid NCAs followed by its ROP using amino-terminated synthetic polymers to polypeptide-polymer block copolymer conjugates. 28 Thus, several different techniques have been employed to synthesize polypeptide/ peptide-polymer conjugates of various polymers and peptides and investigated their self-aggregation behavior in different solvents.…”

Conformation–function relationships for the comb-shaped polymer pOEGMA

“…The hydrodynamic radius of the micelles did not depend on polymer concentration, suggesting that the micelles formed via the closed association model. While micelles of P9 were insensitive to heating, those formed with P23 shrank slightly between 25 and 60 • C. In an interesting example, Trzcinska et al [50] showed that heating a solution of P2 bearing a terminal hydrophilic pentapeptide unit resulted in the formation of spherical mesoglobules. The sizes of the aggregates were easily controlled by changing the concentration and heating rate.…”