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

A living topochemical ring-opening polymerization (ROP) of achiral amino-acid N-carboxyanhydrides (NCAs) is reported. Single crystals of the NCAs of α-aminoisobutyric acid (Aib) and 1-aminocyclohexanecarboxylic acid (ACHC) were grown, allowing a ring-opening polymerization macroscopically induced by amines. The single crystals could be polymerized at temperatures from 25-50 °C after physically contacting the amine-based initiator with the crystals. Topochemical polymerization of the crystals was proven by MALDI-ToF MS and XRD, generating polymers with chain lengths of up to 40 units and a complete affixation of the initiating amine at the polymer's head. Due to the proper alignment of the reacting groups in the crystal, longer polymer chains with improved purities can be reached, as chain-transfer is reduced as compared to solution polymerization. Simple purification of the polymers can be achieved by separation of the unreacted NCA via dispersion in acetonitrile. Overall, this method enables the preparation of polymers with higher chain length and purities at mild conditions, finally demonstrating a crystal-based ring opening polymerization.

Secondary Structures in Synthetic Poly(Amino Acids): Homo- and Copolymers of Poly(Aib), Poly(Glu), and Poly(Asp).

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. A special focus is directed on the folding in hybrid-polymers consisting of oligo(amino acids) and synthetic polymers. Being part of the SFB TRR 102 "Polymers under multiple constraints: restricted and controlled molecular order and mobility" this overview is embedded into the cross section of protein fibrillation and supramolecular polymers. As polymer- and amino acid folding is an important step for the utilization and design of future biomolecules these principles guide to a deeper understanding of amyloid fibrillation.

Novel 12-hydroxydehydroabietylamine derivatives act as potent and selective butyrylcholinesterase inhibitors.

The skeleton of the diterpene dehydroabietylamine was modified, and a set of 12-hydroxy-dehydroabietylamine derivatives was obtained. The compounds were screened in colorimetric Ellman's assays to determine their ability to act as inhibitors for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). Additional investigations concerning the enzyme kinetics were performed and showed 12-hydroxy-N-(4-nitro-benzoyl)dehydroabietylamine (13) and 12-hydroxy-N-(isonicotinoyl)dehydroabietylamine (17) as selective BChE inhibitors holding good inhibition constants Ki = 0.72 ±â€¯0.06 µM and Ki = 0.86 ±â€¯0.19 µM, respectively.

Syntheses of C-ring modified dehydroabietylamides and their cytotoxic activity.

Due to their auspicious pharmacological efficacy as future drug candidates, natural products have been attracting scientific interest for centuries. An interesting field of research concerns the natural product class of terpenes. In this regard, a multitude of studies have already shown their promising biological potential. Therefore, a set of 27 derivatives of the diterpene dehydroabietylamine was synthesized, focusing on C-ring modifications and the derivatization of the amino moiety at C-18. Subsequent screening of the compounds in colorimetric sulforhodamine B-assays revealed an in vitro cytotoxicity especially towards malignant cell line MCF7. Particularly, 12-hydroxy-N-(isonicotinoyl)dehydroabietylamine and N-(4-methoxybenzoyl)dehydroabietylamine showed good cytotoxic activities (EC50 (MCF7) = 4.3 ±â€¯0.2 µM and EC50 (MCF7) = 4.5 ±â€¯1.5 µM, respectively) and significant selectivities (SI = 6.2 and SI = 8.8, respectively) towards malignant cell lines.