A Living Topochemical Ring-Opening Polymerization of Achiral Amino Acid N-Carboxy-Anhydrides in Single Crystals

Rohmer, M. et.al., Chemistry – A European Journal2023, e202302585, e202302585, https://doi.org/10.1002/chem.202302585

The single-crystal ring-opening polymerization of α-aminoisobutyric acid- (Aib) and 1-aminocyclohexanecarboxylic acid- (ACHC) N-carboxyanhydrides (NCAs) is reported. Topochemical, living ring-opening polymerization (ROP) of these achiral amino-acid NCAs produces polymers of highest purity with increased chain length and high end-group fidelity as compared to conventional solution polymerization. © 2023 The Authors. Chemistry – A European Journal published by Wiley-VCH GmbH

Secondary Structures in Synthetic Poly(amino acids): Homo- and Copolymers of Poly(Aib), Poly(Glu) and Poly(Asp)

Rohmer, M. et al., Macromolecular Biosciences, 2023, 2200344,


The secondary structure of poly(amino acids) is an excellent tool for controlling and understanding the functionality and properties of proteins. In this perspective article the secondary structures of the homopolymers of oligo- and poly-glutamic acid (Glu), aspartic acid (Asp), and α-aminoisobutyric acid (Aib) are discussed. Information on external and internal factors, such as the nature of side groups, interactions with solvents and interactions between chains is reviewed. As polymer- and amino acid folding is an important step for the utilization and design of future biomaterials useful for cell-adhesion and embedding, such hybrid materials open a future perspective for biomedicines. © 2023 The Authors. Macromolecular Bioscience published by Wiley‐VCH GmbH.

Inhibition of the fibrillation of amyloid Aβ1-40 by hybrid- lipid-polymer vesicles

Sen, N. et al., Macromolecular Bioscience, 2023, 2200522, DOI:10.1002/mabi.202200522

The transformation of functional proteins into amyloidic plaques is responsible for the impairment of neurological functions in patients fallen victim to debilitating neurological conditions like Alzheimer’s, Parkinson’s, and Huntington’s diseases. We investigate the influence of lipid hybrid-vesicles on alterations of the nucleation process and thus early phases of Aβ1-40 fibrillation. Hybrid-vesicles (±100 nm) are prepared by incorporating variable amounts of cholesterol-/glycerol-conjugated poly(di(ethylene glycol)macrylates)n polymers into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membranes. Such polymers, when embedded in hybrid-vesicles (up to 20%) significantly prolonged the fibrillation lag phase (tlag) compared to a small acceleration in the presence of DOPC vesicles, irrespective of the amount of polymers inside the hybrid-vesicles. © 2023 The Authors. Macromolecular Bioscience published by Wiley‐VCH GmbH.

Bioinspired Synthetic Polymers-Based Inhibitors of Alzheimer’s Amyloid-β Peptide Aggregation

Rupali, J. B. et al., Polymer Chemistry, 2023, 392-411,


Alzheimer’s disease (AD) is a progressive neurodegenerative disease with no current cure and limited treatment solutions, wherefore discovering of novel therapies remains a global challenge in biopharmaceutical industries. This review article aims to summarize articles documenting synthetic polymer-based inhibitors of Aβ aggregations and highlight their potential as promising AD therapeutic agents. Published with a permission of the Royal Society of Chemistry 2023.

Modulating the fibrillization of parathyroid-hormone (PTH) peptides: azo-switches as reversible and catalytic entities

Paschold, A., et al. Biomedicines, 2022, DOI:https://doi.org/10.3390/biomedicines10071512

We here report a novel strategy to control the bioavailability of the fibrillizing parathyroid hormone (PTH)-derived peptides, where the concentration of the bioactive form is controlled by an reversible, photoswitchable peptide. We embed the azobenzene derivate 3-{[(4-aminomethyl)phenyl]diazenyl}benzoic acid (3,4′-AMPB) into the PTH-derived peptide PTH25–37 to generate the artificial peptide AzoPTH25–37 via solid-phase synthesis. The trans-form of AzoPTH25–37 fibrillizes similar to PTH25–37, while the cis-form of AzoPTH25–37 generates only amorphous aggregates. The approach reported here is designed to control the concentration of PTH-peptides, where the bioactive form can be catalytically controlled by an added photoswitchable peptide.

Chiral amines as initiators for ROP and chiral induction on poly(2-aminoisobutyric acid) chains

Rohmer, M.. et. al. Polymer Chemistry, 2021, 12, 6252-6262, DOI: 10.1039/D1PY01021B

2-Aminoisobutyric acid (Aib) is a prominent achiral amino acid known for its helical building properties, generating left- and right-handed helices without any preference. We here report on several short chain poly(Aib)s synthesized by ring opening polymerization (ROP) of Aib-N-carboxy-anhydrides (Aib-NCA) with structurally different chiral amines acting as both, initiator and chiral induction agent. By adding a chiral center at the C-terminus of the polymer chain we can control the direction of the screw sense, since the polymers are adopting the chirality of the initiator following the sergeant-and-soldier principle. Variation of the solvent from hexafluoroisoropanol (HFIP) to water resulted in a significant change of CD signals, featuring a surprising aggregation of the poly(amino acids) into globular aggregates in water in the range of 50 to 200 nm, which accounts for changes in chiral induction. Published with a permission of the Polymer Chemistry 2021.

Membrane Anchored Polymers Modulate Amyloid Fibrillation

Sen, N. et. al., Macromolecular Rapid Communication, 2021, 2100120, https://doi.org/10.1002/marc.202100120

We here report on the influence of conjugates fabricated from lipid anchors (cholesterol, diacylglycerol) and hydrophilic polymers on Aβ1-40 fibrillation, aiming to understand the impact of polymers cloud point temperature (Tcp) and its hydrophobic tails on the amyloid fibrillation. Novel lipid-polymer conjugates, consisting of poly(oligo(ethylene glycol)macrylates) and hydrophobic groups (diacylglyceryl-, cholesteryl-, octyl-, decyl-, hexadecyl-) as anchors are synthesized  via RAFT polymerization, allowing to tune the hydrophilic-hydrophobic profile of the conjugates. Hydrophobic lipid-anchors are significantly delaying fibrillation (both lag, tlag and half times, t1/2), observing similar fibrillar structures via TEM when compared to native Aβ1-40. © 2021 The Authors. Macromolecular Rapid Communications published by Wiley‐VCH GmbH

Peptide-induced RAFT polymerization via an amyloid-ß17-20 -based chain transfer agent

Kumar, S., et al. Soft Matter, 2020, 16,6964-6968, DOI: 10.1039/D0SM01169J

We here describe the synthesis of a novel  peptide/polymer-conjugate, embedding the amyloid-β (Aβ) protein core sequence Leu-Val-Phe-Phe (LVFF, Aβ17-20) via RAFT polymerization. Based on a novel chain transfer-agent, the “grafting-from” approach effectively generates the well-defined peptide-polymer conjugates with appreciably high monomer conversion rate, resulting in mechanically stiffer peptide-functional cross-linked polymeric hydrogels. Reproduced by permission of The Royal Society of Chemistry 2020.

Bifunctional Peptide-Polymer Conjugates Based Fibers via a One-Pot Tandem Disulfide Reduction Coupled to a Thio-Bromo “Click” Reaction

Kumar, S., et al. ACS Omega, 2020, 5 (30) 19020-19028 https://doi.org/10.1021/acsomega.0c02326

In view of the potential applications of fibers towards material sciences and biomedicine, an effective synthetic strategy is described to construct the bi-headed peptide-conjugate FFFF-PEG-FFFF (Mn,GPC= 3800 g mol-1, Ɖ = 1.10) via a one-pot, tandem–disulfide-reduction coupled to a thio-bromo“click” reaction for supramolecular self-association in solution. The conjugate was investigated via transmission electron microscopy to exploit supramolecular fibril formation and solvent dependent structuring into macroscale fibers via fibril-fibril interactions and inter-fibril cross-linking induced bundling. This synthetic approach opens the way for a simplified synthesis of PEG-containing peptide conjugates. Copyright © 2020 American Chemical Society

Tuning layered superstructures in precision polymers.

Danke, V., et al. Scientific Reports 2020, 12119, https://doi.org/10.1038/s41598-020-68927-x

An approach to influence and control layered superstructures by varying the methylene sequence length between two consecutive functional groups in linear precision polymers containing 2,6-diaminopyridfine (DAP) group is presented. Occurrence of different layered structures depending on crystallization conditions, methylene sequence length as well as defect type is explained by a competition of H-interactions between the DAP groups and the van der Waal forces between the hydrophobic methylene groups. Reproduced with permission. Copyright© 2020, Springer Nature.