Poly block copolypeptides

The mechanism of the polymerization of NCA with tertiary amine is still controversial. Mori and Iwatsuki claim that the true initiator is the primary amino group formed by hydrolysis of the NCA with contaminated water and that tertiary amine forms a complex with the NCA and accelerates the addition reaction37 . Harwood et al. confirmed the propagating carbamate by NMR in polymerization initiated with a strong base37 . The successive addition of NCA to the polymer end catalyzed with a strong base affords an alternative procedure for the synthesis of block copolypeptides. Block copolypeptides of poly(oxyethylene) were prepared by triethyl amine catalyzed polymerization of NCA in the presence of poly(oxyethylene)bis-eMoroformate38 . 

Fig. 1 Vesicle construct formed from poly(L-lysine)-i)-poly(L-leucme) polypeptides where the poly(L-leucine) block corresponds to the a-helical hydrophobic segments and the poly (L-lysine) block corresponds to the random coil hydrophilic segments. Note that this is one specific example and not all vesicle constructs have a-helical and random coil blocks. Moreover, the amphiphilic copolymer can be comprised of either a pure block copolypeptide or a macromolecule consisting of a polypeptide and another type of polymer. Adapted from [20] with permission. Copyright 2010 American Chemical Society...

Living NCA polymerizations of a wide variety of monomers have also been initiated with transition metal catalysts, allowing the preparation of proteins and block copolypeptide-sin high yield with low polydispersity. NCA catalysts have also been employed to produce low-polydispersity protein-synthetic polymer hybrid materials. Using a bifunctional initiator in nickel-mediated NCA polymerization followed by ATRP, poly(Y-benzyl-L-glutamate-l7-methyl methacrylate) (PBLG-b-PMMA) was prepared with polydispersity in the range of 1.2-1.4. ... 

Recently, synthetic or natural polypeptides have been created or modified to serve as sihca condensation templates. Examples of these include the poly(amino acids) [79], the diatom-derived R5-peptide [66], chimeric polypeptides [64, 67], block copolypeptides [71, 72, 75, 80], lanreotide [63] and even the naturally occurring protamine [65]. These polypeptides have been used to produce a variety of sihca shapes and sizes, which can be tuned to perform a variety of applications, including transport and the separation of encapsulated materials [62], or potentially for dmg dehvery [73]. 

A second method for assigning the A-B and B-A bonds in copolypeptides is by the so-called guest-host polypeptides which are prepared from a 1 50 ratio of 15N enriched monomer A natural abundance monomer B. Chemical shifts of the 15N enriched guest-monomers (A ) flanked by blocks of B monomers represent the B-A bonds in copolypeptides. Numerous copolypeptides having the general structure (Bn)-A -(Bm) were synthesized and analyzed as models for syndiotactic sequences in the spectra of poly (D,L-amino acids) (4, 17). 

To address this issue, Hadjichristidis developed the synthesis of 3- and 4-arm star copolypeptides by high-vacuum polymerization using the core-first method. They prepared 3-arm stars containing poly(Z-Lys) and poly(Bn-Glu) block copolymers that were simultaneously grown off of a 2(aminomethyl)-2-methyl-1,3-propanediamine initiator core (Scheme 2). This method produced well-defined star copolymers with narrow molecular weight distributions. Attempts to prepare 4-arm star copolymers... 

In 2004, Deming s laboratory studied the roles of chain length and block composition on the assembly of uncharged diblock copolypeptide amphiphiles of the general structure poly(77e-2-[2-(2-methoxyethoxy)ethoxy]acetyl-L-lysine)-Z loc -poly(L-leucine), or [88]. These diblock copolypeptide amphiphiles... 

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