Photochromic cyclic dipeptides as biocompatible smart materials

• Applicant: Privatdozent Dr. Zbigniev Pianowski
• Subject Area: Biological and Biomimetic Chemistry ; Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2016 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 317869603

• Final Report Year: 2025

Final Report Abstract

In this project, we explored the use of photochromic cyclic dipeptides in the biological context, particularly as light-triggered smart materials. We developed biocompatible hydrogels that show green- or red-light-driven contraction or liquefaction, and concomitant release encapsulated cargo such as small bioactive molecules, or proteins without denaturation. Therein, we developed composite hydrogels stabilized with alginate via Coulomb interactions. As a result, the photochromic gelating component could be seriously redcued, without comprimising the overall mechanical stability, and the component ratio can be easily changed for fine-tuning of the material. These systems enable room-temperature encapsulation of sensitive cargo, such as proteins, which can be later released with light in a controllable manner. They can be also treated with aqueous solutions of calcium salts, where the metal ion expels the photochromic DKP, leaving pure, insoluble, and mechanically stable calcium alginate gel in the shape, that may be predefined with light. Furthermore, we tested if our arginine-decorated cyclic dipeptides can form supramolecular cell-penetrating peptides in a photoreversible manner, however that system requires serious optimization. Finally, we discovered a new type of biocompatible peptide-derived molecular photoswitch – hemipiperazine – which opened up a new avenue for photomodulation of biological systems, including cytotoxicity and embryonal development, as well as for design of photoresponsive materials.

Publications

• Hemipiperazines as peptide-derived molecular photoswitches with low-nanomolar cytotoxicity. Nature Communications, 13(1).
  Kirchner, Susanne; Leistner, Anna-Lena; Gödtel, Peter; Seliwjorstow, Angelika; Weber, Sven; Karcher, Johannes; Nieger, Martin & Pianowski, Zbigniew
  
• Molecular Photoswitches. Wiley.
  Pianowski, Zbigniew L.
  
• Photopharmacology of Antimitotic Agents. International Journal of Molecular Sciences, 23(10), 5657.
  Kirchner, Susanne & Pianowski, Zbigniew
  
• Reversible photodissipation of composite photochromic azobenzene-alginate supramolecular hydrogels. RSC Advances, 12(8), 4771-4776.
  Leistner, Anna-Lena; Kistner, David Georg; Fengler, Christian & Pianowski, Zbigniew L.
  
• Smart Photochromic Materials Triggered with Visible Light. European Journal of Organic Chemistry, 2022(19).
  Leistner, Anna‐Lena & Pianowski, Zbigniew L.
  
• Heterocyclic Hemipiperazines: Water‐Compatible Peptide‐Derived Photoswitches. Chemistry – A European Journal, 29(26).
  Gödtel, Peter; Starrett, Jessica & Pianowski, Zbigniew L.
  
• Molecular Syringe for Cargo Photorelease: Red‐Light‐Triggered Supramolecular Hydrogel. Chemistry – A European Journal, 29(65).
  Leistner, Anna‐Lena; Most, Mario M. & Pianowski, Zbigniew L.
  
• Non-established photoswitchable organic systems. Photochemistry, 436–454.
  Pianowski, Z.
  
• Heterocyclic Hemipiperazines: Multistimuli‐Responsive Switches and Sensors for Zinc or Cadmium Ions. Chemistry – A European Journal, 30(53).
  Schäfer, Valentin & Pianowski, Zbigniew L.
  
• Reversible Influence of Hemipiperazine Photochromism on the Early Development of Zebrafish Embryo. ChemBioChem, 25(8).
  Seliwjorstow, Angelika; Takamiya, Masanari; Rastegar, Sepand & Pianowski, Zbigniew
  
• Visible Light‐Triggered Supramolecular Hydrogel Based on Cyclic Dipeptides Stabilized with Coulomb Interactions. Macromolecular Materials and Engineering, 309(5).
  Seliwjorstow, Angelika; Bach, Marius; Kirchner, Susanne; Palloks, Sarah & Pianowski, Zbigniew L.
  
• Glucose-derived receptors for photo-controlled binding of amino acid esters in water. Communications Chemistry, 8(1).
  Most, Mario M.; Boll, Linus B.; Gödtel, Peter; Pianowski, Zbigniew L. & Lewandowski, Bartosz