Water-soluble peptides that adopt stable helical conformations are attractive motifs because of their importance in basic science and their broad utility in medicine and biotechnology. Incorporating charged amino-acid residues to improve peptide solubility, however, usually leads to reduced helical stability because of increased side-chain charge repulsion, reduced side-chain hydrophobicity and the disruption of intramolecular hydrogen bonding. Here, we show that water-soluble, ultra-stable α-helical polypeptides can be produced by elongating charge-containing amino-acid side chains to position the charges distally from the polypeptide backbone. The strategy has been successfully applied to the design and synthesis of watersoluble polypeptides bearing long, charged side chains and various functional moieties that possess unusual helical stability against changing environmental conditions, including changes in the pH and temperature and the presence of denaturing reagents.
The inclusion complexation between beta-CD (beta-cyclodextrin) and adamantyl group (ADA) is used as a driving force in constructing polymeric micelles. The micelles composed of a hydrophobic core of PtBA-ADA and a hydrophilic shell of PGMA-CD show unique properties due to the presence of beta-CDs on the micellar surface. The micelles can be converted to hollow spheres of PGMA-CD networks. The hollow spheres possess a central hole in the size of submicrometers and many cavities of beta-CDs of 0.7 nm on the surface.
We report here the integration of ring-opening metathesis polymerization (ROMP) and ring-opening polymerization of the amino acid N–carboxyanhydride (NCA) to allow facile synthesis of brush-like polymers containing polypeptide as the brush side chains. ROMP of N–trimethylsilyl norbornenes rendered the preparation of poly(norbornene)s bearing pendant N-TMS groups. With no need to purify the resulting polymers, such macromolecular initiators could subsequently initiate controlled NCA polymerizations. Brush-like poly(norbornene)s with grafted polypeptides or block copolypeptides were readily obtained with controlled molecular weights and narrow molecular weight distributions. Because numerous ROMP and NCA monomers are widely available, this novel polymerization technique will allow easy access to numerous brush-like hybrid macromolecules with unprecedented properties and broad applications.
We report a new methodology for the synthesis of polymer-drug conjugates from “compound”—all in one—prodrug monomers that consist of a cyclic polymerizable group that is appended to a drug through a cleavable linker. We show that organocatalyzed ring-opening polymerization can polymerize these monomers into well-defined polymer prodrugs that are designed to self-assemble into nanoparticles and release drug in response to a physiologically relevant stimulus. This method is compatible with structurally diverse drugs and allows different drugs to be copolymerized with quantitative conversion of the monomers. The drug loading can be controlled by adjusting the monomer(s) to initiator feed ratio and drug release can be encoded into the polymer by the choice of linker. Initiating these monomers from a polyethylene glycol macroinitiator yields amphiphilic diblock copolymers that spontaneously self-assemble into micelles with a long plasma circulation, which is useful for systemic therapy.
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