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ERC

SIP Report Summary

Project ID: 305064
Funded under: FP7-IDEAS-ERC
Country: Germany

Final Report Summary - SIP (SPECIFICALLY INTERACTING POLYMERS– From Selective Adhesion toward Specific Recognition)

The ERC research project “Specifically Interacting Polymers” (SIP) endeavoured to investigate means toward synthetic polymers that are capable of specific interactions and exploit those as a platform to develop next generation, highly purpose adapted polymers. The potentials of these novel type of macromolecules was demonstrated by addressing relevant materials science applications such as drug structure specific solubilization of insoluble drug molecules, surface selective functionalization of printed microstructured paper and filler specific compatibilizers for interface management in composite materials.
A general approach has been established leading in the first step to efficient design strategies for peptide-polymer conjugates, which can be considered as 1st generation Specifically Interacting Polymers. Combinatorial means were broadly exploited to identify and select peptide sequences from large peptide libraries for sequence specific interactions with desired targets such as small molecules, surfaces, or internal material interfaces. In three research Boxes (RBox1-3) highly relevant interdisciplinary application areas of functional polymers in biomedicine, soft matter organization and materials design have been addressed. After in-depth analysis of the identified peptides, sequence-function relationships have been revealed by studying sets of systematic sequence analogues.
The gained knowledge on relevant sequence positions and residues as well as minimal binding motifs was employed to guide the design of 2nd generation Specifically Interacting Polymers, which have been constituted from segments of sequence-defined polymers. The precision polymer segments were composed from fully synthetic monomer alphabets and could mimic aspects of specific interactions found in the selected peptide sequences. The general SIP strategy “learning from peptides & realizing with synthetic polymers” has been demonstrated and added innovative possibilities to adapt precision polymers toward applications.
In RBox1 “Specific Solubilizers” have been realized to overcome unfavored pharmacological profiles of problematic drugs or high potential lead compounds. Proof of concept was demonstrated on m-THPC, a sensitizer drug for the photodynamic cancer therapy. Specifically tailored solubilizers render the insoluble drug water soluble, significantly improving the availability of the drug and enabling programming of a transition from silent non-active transport form to the drug in its active state. Remarkably, structure specific interactions could be found in a study on identifying host sequences for a set of structurally related drugs. Advanced screening procedures led to accelerated drug release by reductive triggers and peptide–based drug binders were implemented into a transdermal delivery system. The concept has been shown for fluorescent drugs and non-fluorescent drugs such as promising anti-Alzheimer active lead-structures. The understanding of interaction modes in solubilizer/drug complexes provided sequence-property relationships to guide the design of 2nd generation SIPs offered in some cases superior properties to accommodate drugs and exhibit adjustable release profiles.
In RBox2, sets of “Specific Surface Recognizers”, could be identified that bind specifically either to plain paper or to toner on printouts of office laser printers. A flexible and inexpensive strategy to generate functional 2D-micro patterned paper surfaces was demonstrated, allowing structures and gradients to be printed with laser printers and effectively converting these patterns into functional structures. The functional 2D-micro patterned paper surfaces were investigated as substrates for localized biomimetic crystallization or topological antibacterial surfaces. Specific binders for multicolor printouts have been addressed delivering promising results for material specific coatings. Binding motif analysis on peptide-based toner/cellulose selective coatings were conducted to allow for the identification of suitable motifs, which could be mimicked as 2nd generation SIPs. The established cost-effective access to functionalized-2D-patterns by surface specific functionalization of laser printouts on printing paper have been ultimately applied to investigate the printing process of sets of electrodes for selective sensor devices to target high selectivity sensors.
In RBox3 “Specific Compatibilizers” have been tailor-made to specifically stabilize internal material interfaces in hybridmaterials. Peptidic-based binders for inorganic or organic nanoparticle fillers were selected via phage display. The resulting peptide-polymer conjugates proved to act as de novo stabilizers for nanoparticle states and compatibilize those particles effectively into a polymer matrix by managing the internal material interfaces of inorganic-organic but also organic-organic composites. The concept has been demonstrated with applicable composites, combining MgF2 nanoparticles and PCL to provide remarkable increases in both Young-Modulus and toughness. Moreover, SIP compatibilizers significantly enhanced the 3D printing processability of those composite materials. 2nd generation SIP’s could effectively mimic the underlying binding motifs. The importance of internal interfaces is well known from biomaterials but the exploitation in synthetic composites is still at the onset and SIP compatibilizers offer a capable tool to integrate the specific interface management into material design concepts of high-performance composites.
Abstracting the underlying concepts of specific-binding of peptides toward different targets enabled the team of the SIP project to realize 2nd generation SIP’s from fully synthetic monomer alphabets with defined monomer sequences and high information contents. These precision polymers allow one to endeavour toward next-generation biomimetic materials and precisely tailored functional polymers that offer exciting new possibilities and promising functions.

Reported by

HUMBOLDT-UNIVERSITAT ZU BERLIN
Germany
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