Macromolecular Rapid Communications

Cover image for Vol. 35 Issue 8

Special Series: Polymer Conjugates

Under the guest-editorship of Harm-Anton Klok this series publishes in an on-going fashion invited articles by leading researchers with a special focus on polymer conjugates.


Molecular Bottlebrushes with Polypeptide Backbone


Yu Liu, Ping Chen, and Zhibo Li*

Molecular bottlebrushes display unique macromolecular architectures with interesting properties and potential applications. Molecular bottlebrushes with polypeptides are of particular interest because they synthetically mimic natural proteoglycan. It is a challenging task to make well-defined polypeptide bottlebrush with tunable and variable side chain. Zhibo Li and co-workers (Institute of Chemistry, Chinese Academy of Sciences, Beijing) report the design and synthesis of molecular bottlebrush bearing poly-L-lysine as a backbone. A new bromo-functionalized homopolypeptide is synthesized via ring-opening polymerization, which is then used as an efficient macroinitiator for atom transfer radical polymerization of side chains to give well-defined polypeptide bottlebrushes.

Macromol. Rapid Commun., DOI: 10.1002/marc.201100649


A Plethora of Block Copolypeptides


Gijs J. M. Habraken, Andreas Heise, and Paul D. Thornton*

While natural polypeptides with a specific sequence of amino acid constituents adopt structural motifs such as α-helices, β-sheets, and random coils through non-covalent interactions, the occurrence of these features in synthetic polymers is rare. However, extended (homo)polypeptides consisting of a limited number of amino acids that lack a specific sequence can be created by N-carboxyanhydride ring-opening polymerization (NCA ROP) as a synthetically straightforward methodology to afford polypeptidic materials that may adopt secondary structures analogous to those of natural proteins. Such structures may offer biocompatibility in addition to stimuli-responsive and self-assembly properties. Paul D. Thornton and co-workers from Dublin City University offer an insight into contemporary synthetic approaches toward NCA ROP before highlighting a number of block copolypeptide architectures.

Macromol. Rapid Commun., DOI: 10.1002/marc.201100730


3D Arrangement of Short DNA Oligonucleotides at Surfaces


Olivier Y. F. Henry,* Ahmed D. Mehdi, Sinead Kirwan, Josep Luis Acero Sanchez, and Ciara K. O'Sullivan*

The need for new approaches to realize rapid and highly sensitive diagnostic devices and environmental monitoring systems requires ever more effective surface chemistries. The arrangement of short DNA oligonucleotides at surfaces plays a major role in the overall surface binding capacity of the complementary sequence present in a sample. Henry, O'Sullivan and co-workers incorporate short DNA oligonucleotide into acrylamide brushes via surface initiated ATRP in an attempt to increase the DNA surface density by building 3D molecular architectures. The morphology and the performance of the resulting polymer are characterized by surface plasmon resonance and ATR-FTIR spectroscopy, as well as MALDI-TOF analysis, and compared to monolayers of thiolated DNA strands. This new approach offers a promising alternative to SAM-based nucleic acid and aptamer sensors and could enable the realization of more complex soft materials of controlled architecture capable of both recognition and signaling by including additional optically or electrochemically active moieties.

Macromol. Rapid Commun., DOI: 10.1002/marc.201100317


Grafting-from and RAFT Polymerization - A Powerful Combination

polymconj_32_4_2_Sumerlin.jpgMing Li, Hongmei Li, Priyadarsi De, and Brent S. Sumerlin*

Modification of biomacromolecules with synthetic polymers is an effective means to enhance the solubility, biocompatibility, stability and activity of proteins, nucleic acids, and polysaccharides, potentially enabling a variety of new biotechnology applications. The group of Brent Sumerlin (Dallas, USA) presents the first example of combining the grafting-from and RAFT technique, providing a new method for the preparation of block copolymer polymer-protein conjugates. The resulting conjugates prepared by two consecutive grafting-from reactions via RAFT polymerization exhibit thermoresponsive behavior due to the temperature-sensitivity of the PNIPAM block.
This article is addtionally featured on MaterialsViews.

Macromol. Rapid Commun., DOI: 10.1002/marc.201000619


Amine-Reactive PEGylated Nanoparticles for Potential Bioconjugation


Guillaume Delaittre,* Gemma Justribo-Hernandez, Roeland J. M. Nolte, and Jeroen J. L. M. Cornelissen*

Functionalization of the surface of nanoparticles (NPs) is a highly important field, especially regarding their application as transport agents in drug delivery systems. Amongst others, a suitable way to obtain polymeric NPs is through the self-assembly of amphiphilic block copolymers. If the watersoluble block contains a specific moiety then the NPs will also be functionalized on their surface. Guillaume Delaittre, Jeroen Cornelissen and co-workers have developed a route towards amine-reactive polymeric NPs by using an amphiphilic block copolymer, which contains an N-hydrosuccinimidyl (NHS) ester at its water-soluble end. The reactivity of the NPs was evidenced by reacting them with primary amines, including a fluorescent dye. The activated ester remained stable throughout all synthetic steps and a nearly quantitative coupling efficiency was obtained. This work represents the first example of a PEGylated nanoparticular system with reactivity towards amines.

Macromol. Rapid Commun., DOI: 10.1002/marc.201000365


Biologically Inspired Coiled Coil Linkers in Polymer-Drug Conjugates

polymconj_32_1_1_klok.jpgBojana Apostolovic, Samuel P.E. Deacon, Ruth Duncan, and Harm-Anton Klok*

Polymer-drug conjugates are nanomedicines that consist of a water-soluble, biocompatible polymer backbone to which multiple copies of a drug molecule are bound. The linkers connecting the polymer and the drug can respond to external stimuli (pH or the presence of enzymes) and thereby trigger the release process of the drug. Harm-Anton Klok and co-workers introduced a conceptually novel class of polymer-drug conjugates in which the drug molecules are attached to the polymer via a noncovalent, so called coiled coil motif, which is formed by heterodimerization of two complementary peptide strands, one of which is attached to the polymer carrier and the other to the drug. In this study, further insight into the cell uptake and trafficking behavior of these nanomedicines is obtained using cytotoxicity and FACS experiments. The results provide important information for the design of future polymer-drug conjugates.

Macromol. Rapid Commun., DOI: 10.1002/marc.201000434


A Playground for Novel Copolymers

polymconj_31_19_1_Lecommandoux.jpgS. Lecommandoux* and C. Schatz*

Chemical pathways to polysaccharide block copolymers cover all the range from enzymatic polymerization to the polymerization of a synthetic block from an end-functionalized polysaccharide block (via ring-opening or radical polymerization) and to the end-to-end coupling of polysaccharide and synthetic blocks. These copolymers display physicochemical properties close to those of synthetic block copolymers and combine them with an added value in the form of biodegradability, biocompatibility, or in some cases bioactivity. Therefore, these polysaccharide conjugates might represent a new class of biomaterials for diagnosis tests, vaccine formulations, and also for the design of drug delivery systems with targeting properties. S. Lecommandoux and C. Schatz (Bordeaux, France) provide with their timely review an excellent addition to the literature on sugar-based polymers that will definitively constitute an important resource for the scientific community working in the field

Macromol. Rapid Commun., DOI: 10.1002/marc.201000267


How to Purify Proteins Using Polymers

polymconj_31_19_2_Maynard.jpgChien-Wen Chang, Thi H. Nguyen, and Heather D. Maynard*

Proteins are important therapeutics and essential agents to study biological processes. Critical to these applications are efficient and inexpensive methods to purify these biomolecules. Heather Maynard and co-workers (UCLA) introduce a single-step method to "pull down" or isolate proteins that contain a common genetic tag, glutathione S-transferase (GST). Glutathione (GSH, a natural reductant found in living cells) reversibly interacts with GST via precise molecular recognition in aqueous solution. The researcher synthesized a pyridyl disulfide-poly(N-isopropylacrylamide) (pNIPAAm) that could be conjugated to GSH with high efficiency (95% in 30 minutes). GST was successfully thermoprecipitated upon heating the GSH–pNIPAAm above the lower critical solution temperature. Due to its simplicity and high efficiency, this method holds great potential for large-scale purification of GST-tagged proteins.

Macromol. Rapid Commun., DOI: 10.1002/marc.201000333


Studying Controlled Release from Liposomes Using Polymer-Enzyme Conjugates

polymconj_31_19_3_Griffith.jpgElaine L. Ferguson,* Edoardo De Luca, Richard K. Heenan, Stephen M. King, and Peter C. Griffiths*

Liposomes (vesicles) are advanced drug delivery systems and as such increasingly being used to improve the therapeutic profile of conventional chemotherapy drugs. Polymer enzyme liposome therapy (PELT) utilizes a polymer-bound enzyme to trigger the release of drugs encapsulated within a liposome. P. C. Griffith, E. L. Ferguson, and co-workers use small-angle neutron scattering (SANS) to quantify the detailed structure of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes and perturbations in that structure induced by phospholipase A2 (PLA2). They could show that the PLA2-induced hydrolysis of the DPPC – and the associated rupture of the liposome and the release of the enclosed material – may be controlled through masking with dextrin. Accordingly, the viability of using such a combinatorial nano-medicine approach as a general route for the controlled delivery of poorly soluble therapeutic molecules is demonstrated.

Macromol. Rapid Commun., DOI: 10.1002/marc.201000241


Cell Receptor-Responsiveness and Targeted Delivery of Growth Factors


Sung Hye Kim and Kristi L. Kiick*

Engineered delivery systems for bioactive signaling molecules, such as growth factors (GFs), have been extensively studied, because these vehicles provide stabilization of GF activity and prolonged delivery. Kristi Kiick's group has studied cell receptor-responsiveness and targeted delivery of the vascular endothelial growth factor (VEGF) from non-covalently assembled, heparinized polymeric hydrogels. The hydrogel is formed via specific non-covalent interactions between 4-arm star poly(ethylene glycol)-heparin and dimeric VEGF. They could show that growth factor-crosslinked hydrogels can liberate VEGF in response to specific receptors, causing gel erosion and desired cell responses, thus suggesting the potential utility of these materials in therapeutic applications, including targeted delivery.

Macromol. Rapid Commun., DOI: 10.1002/marc.201000130


Bioorganic Nanoobjects of DNA Block Copolymers

polymconj_31_14_3_Herrmann.jpgMukhles Sowwan*, Maryam Faroun, Elad Mentovich, Imad Ibrahim, Shayma Haboush Fikri Emrah Alemdaroglu, Minseok Kwak, Shachar Richter*, and Andreas Herrmann*

Amphiphilic block copolymers comprized of organic polymers and oligonucleotides form micelles in aqueous solution due to microphase separation. These DNA block copolymer (DBC) aggregates are made of a hydrophobic polymer core and a corona of single-stranded DNA. A. Herrmann and co-workers investigate the electrical features of these bioorganic nanoobjects by doping the polymeric core of the micelles with ferrocene molecules. They could show that doping does not alter the size or shape of the micelles but significantly changes their electrical properties, as revealed by electrostatic force microscopy measurements. Their findings may lead to new possibility of using these nanoobjects in e.g. nanoelectronic and sensing applications.

Macromol. Rapid Commun., DOI: 10.1002/marc.200900904


Chemistry Meets Biology

polymconj_31_14_1_klok.jpgHarm-Anton Klok

Biological-synthetic polymer conjugates covalently combine one or more copies of a biomacromolecule (e.g., a peptide sequence) with one or more elements of a synthetic polymer. These hybrid materials allow the synergistical combination of the properties of these different classes of materials and serve to overcome some of their limitations. Although the first peptide-polymer conjugate was already reported in the 50s more recent advances in controlled polymerization techniques and the development of novel and improved chemoselective coupling strategies have pushed this area further ahead lately. This special series on polymer conjugates guest-edited by Harm-Anton Klok (Lausanne, Switzerland), which will publish invited articles from leading scientists, will hopefully further stimulate research in this exciting field.

Macromol. Rapid Commun., DOI: 10.1002/marc.201000182