Beilstein J. Org. Chem. 2015, 11, 2646-2653. DOI:10.3762/bjoc.11.284
Sebastian Nils Fischer, Armin Geyer.
Supporting Information
Abstract Covalent dynamic chemistry is used to mimic the first steps of the highly cooperative fibril formation of Aβ peptides. For that purpose, Aβ peptide pentapeptide boronic acids 1 and 2 were synthesized by solid-phase peptide synthesis and studied in esterification experiments with polyhydroxylated templates. The bis-hydroxylated dipeptide Hot=Tap serves as a template of adjustable degree of oligomerization which spontaneously forms boronic esters with peptides of type 1 and 2. Nuclear magnetic resonance can differentiate between regioisomeric boronic esters and identifies preferred sites of esterification on the dimeric template 9. 2-Formylphenylboronic acid (14) is used to link the parent pentapeptide Leu-Val-Phe-Phe-Ala to the template 16 to obtain threefold boronic ester 17. The miniamyloid 17 assembles from seven components by imine and boronic ester bonds between the peptides and the template. The relative orientation and spacing of the peptides mimic the assembly of peptides in Alzheimer β-amyloids.
Top Heterocycl Chem. 2015, 1-23. Springer Int. Publishing Switzerland. DOI 10.1007/7081_2015_181.
André Wuttke, Armin Geyer.
Abstract This review is dedicated to the fitting and functional characterization of polyhydroxylated amino acids into protein environments, noting that systematic compendia of sugar-derived unnatural building blocks can be found in the literature. This review is focused on the local exchange of two sequential amino acids in a peptide or protein for a polyhydroxylated δ-amino acid in various applications ranging from ligand design to the investigation of protein function. Two general strategies are respectively differentiated that delete and retain the peptide backbone. So-called sugar amino acids (SAAs) exchange one peptide bond for a tetrahydropyran or furan ring. Alternatively, polyhydroxylated bicyclic dipeptides encompass an amide bond within their ring system and become integral parts of the peptide backbone (compare SAA and Xaa = Yaa in Fig. 1). In peptides, these polyhydroxylated ring systems may favor turn and loop conformations, modify polarity, and offer handles for ligation methods. The influence of ring substituents on these heterocycles is discussed with respect to their potential to increase the stability of particular conformations with preferred orientations as well as to mediate supramolecular interactions. In addition, examples of the use of polyhydroxylated ring systems to stabilize standalone peptide hairpins and mediate protein–protein interactions will be presented.
Eur. J. Org. Chem. 2015, 7443-7448. DOI: 10.1002/ejoc.201501179
Matthias Lamping, Sebastian Enck, Armin Geyer
Supporting Information
Front Cover 
Abstract Substitution of a peptide bond for an imine transforms the irreversible macrocyclization of peptides into a reversible process. The inherent cyclization tendency of a linear peptide is then analyzable through the equilibrium between the aldehyde and the imine by virtue of the higher reactivity of the corresponding linear peptide aldehyde. The tryptophan side chain of segetalin A aldehyde forms a 12-membered cyclic indole hemiaminal instead of the 18-membered macrocyclic imine expected. Herein, we analyzed this uncommon hemiaminal that shows that the biosynthesis of cyclic peptides is not necessarily based on linear precursor peptides with a high inherent macrolactamization tendency.
Eur. J. Org. Chem. 2015, 6448-6457. DOI: 10.1002/ejoc.201500724
Matthias Körling, Armin Geyer
Supporting Information
Abstract β-Turns mediate diverse protein recognition processes, although dihedral angle preferences of canonical amino acids limit accessible β-turn geometries. Organic synthesis can go beyond these limitations and either increase the mobility of a β-turn or constrain it inside a bicyclic ring. Nine β-turn dipeptides are studied here in the isolated β-hairpin of the miniprotein Foldon, which is only moderately structured in the absence of the native protein environment. The dipeptide mimetics, which vary the backbone flexibility from linear alkyl chains to bicyclic dipeptides (Hot=Tap), are ranked against each other with regard to their hairpin-stabilizing capacities. NMR-derived parameters and melting temperatures correlate the backbone rigidity of the β-turns with the hairpin population. In contrast to the general expectation, highly populated hairpins are not only observed for rigid dipeptides, but also for selected flexible amino acids in the i + 1 and i + 2 positions of the β-turn.
Eur. J. Org. Chem. 2015, 2382-2387. DOI: 10.1002/ejoc.201500048
Matthias Körling, Armin Geyer.
Supporting Information
Abstract Dissecting proteins into their secondary structure elements (subdomains) should yield discrete peptide epitopes. However, β-hairpins detached from their natural protein environment usually lose their well-defined shape and, consequently, molecular recognition processes, such as antibody binding or protein interactions, are affected significantly. Thus, the isolated central β-hairpin (residues 12–24) of Foldon, the protein domain of this study, relaxes into a multitude of rotamers, although it still fulfills all necessary requirements to fold into a highly twisted shape. Here, two stabilization strategies from either end of the antiparallel strands of the discrete hairpin are opposed to each other, which reconstitute its shape in solution. The local side chain to backbone cyclization by the twist-compatible bicyclic β-turn mimetic Hot=Tap is identified to be superior to macrocyclic disulfide cyclization, which provokes local structural distortions.
Angew. Chem. Int. Ed. 2015, 54, 6364-6369. DOI: 10.1002/anie.201412055
Angew. Chem. 2015, 127, 6462-6467. DOI: 10.1002/ange.201412055
Alexander Ewe, Anita Jansen de Salazar, Katharina Lemmnitzer, Michael Marsch, Achim Aigner, Armin Geyer.
Supporting Information
Abstract Synthetic polyesters are usually composed of monohydroxycarboxylic acids to avoid the problem of regioselectivity during ring-opening polymerization. In contrast, the linear polyester BICpoly contains four secondary OH groups and is nevertheless esterified regioselectively at only one of these positions. Neither the synthesis of the tricyclic monomers nor the ring-opening polymerization requires protecting groups, making BICpoly an attractive novel and biocompatible polymer. BICpoly nanoparticles can be loaded with low-molecular weight drugs or coated onto surfaces as thin films. The release of loaded compounds makes BICpoly an attractive depot for drug release, as shown herein by loading BICpoly with dyes or the cytostatic drug doxorubicin. BICpoly is distinguishable from other polymers by its characteristic pH-dependent degradation.
Beilstein J. Nanotechnol. 2015, 6, 103-110. doi:10.3762/bjnano.6.10
Maryna Abacilar, Fabian Daus, Armin Geyer.
Supporting Information
Abstract Biosilicification sets the standard for the localized in vitro precipitation of silica at low orthosilicate concentrations in aqueous environment under ambient conditions. Numerous parameters must be controlled for the development of new technologies in designing inventive nanosilica structures, which are able to challenge the biological templates. A long neglected requirement that came into focus in the recent years are the cellular techniques of preventing unintentional lithification of cellular structures since numerous cellular components such as membranes, DNA, and proteins are known to precipitate nanosilica. The diatom metabolism makes use of techniques that restrict silicification to an armor of silica around the cell wall while avoiding the petrifying gaze of Medusa, which turns the whole cell into stone. Step by step, biochemistry unveils the hierarchical interplay of an arsenal of low-molecular weight molecules, proteins, and the cytoskeletal architecture and it becomes clearer why the organisms invest much metabolic effort for an obviously simple chemical reaction like the precipitation of amorphous silica. The discrimination between different soluble components in the silicification process (chemoselective silicification) is not only vitally important for the diatom but poses an interesting challenge for in vitro experiments. Until now, silica precipitation studies were mainly focused on the amount, the morphology, and composition of the precipitate while disregarding a quantitative analysis of the remaining soluble components. Here, we turn the tables and quantify the soluble components by 1H NMR in the progress of precipitation and present experiments which quantify the additivity, and potential cooperativity of long chain polyamines (LCPAs) and cationic peptides in the silicification process.
Journal of Chemical Crystallography 2014, 44, 407-414. DOI: 10.1007/s10870-014-0530-6
Mahmoud Al-Refai, Armin Geyer, Michael Marsch, Basem F. Ali.
Abstract The title compound was prepared by the condensation of (E)-1-(2,5-dichlorothiophen-3-yl)-3-(4-methoxy)prop-2-en-1-one and thiourea in the presence of KOH. In the title compound, C34H28Cl16N4O2S4, the asymmetric unit consists of two independent molecules and four independent chloroform molecules. The heterocyclic pyrimidine-2(1H)-thione rings adopt a flattened boat conformation. The methoxyphenyl rings are perpendicular to the pyrimidine-2(1H)-thione rings with dihedral angles of 81.20 and 79.85° in both independent molecules. The dichlorothiophene rings are twisted compared to the pyrimidine-2(1H)-thione rings with dihedral angles of 40.59 and 39.36° in the independent molecules. The methoxyphenyl group has an axial orientation. Intermolecular C–H···S, C–H···O, C–H··· π vertex-to-face intermolecular interactions between chloroform C–H groups and the center of the phenyl rings and extensive Cl···Cl intermolecular interactions are found in the crystal structure. All interactions consolidate a three dimensional network. The molecular structure was further analyzed using spectroscopic methods. Mass ESI-HMRS measurements were performed. The HRESIMS analysis revealed the molecular formula, C15H12Cl2N2OS2, with [M+H]+ and [M+H+2]+ and [M+H+4]+ isotopic clusters characteristic for a dichlorinated compound. The compound was also thoroughly characterized by 1H, 13C, NMR spectra and 2D NMR spectra (COSY, HSQC and HMBC).
S. Fischer, A. Geyer. Filaggrin-Peptide mit -hairpin-Struktur binden Rheuma-Antikörper. Angew. Chem. 2014, 126, 3928-3933.
Filaggrin peptides with -hairpin structure bind rheumatoid arthritis antibodies Angew. Chem. Int. Ed. Engl. 2014, 53, 3849-3853.
A. M. Roeder, Y. Roettger, A. Stuendel, R. Dodel, A. Geyer. Synthetic dimeric A-mimics the complex epitope of human anti-Aautoantibodies against toxic A oligomers. Journal of Biological Chemistry 2013, 288, 27638-27645.
F. Weiher, M. Schatz, C. Steinem, A. Geyer. Silica precipitation by synthetic minicollagenes. Biomacromolecules 2013, 14, 683-687.
M. Deshmukh, S. Singh, A. Geyer. Synthetic adhesive oligopeptides with rigid polyhydroxylated amino acids. Biopolymers 2013, 99, 273-281.
A. Geyer, S. Enck. Approaches to thiazole dipeptides for the synthesis of thiopeptide antibiotics. Targets in Heterocyclic Systems, Chemistry and Properties 2012, 16, 113-127.
A. Geyer. Buchrezension Moleküle aus dem All? Erlebnis Wissenschaft. (ISBN 978-3527328772). Angew. Chem. 2012, 124, 4601.
S. Enck, P. Tremmel, S. Eckhardt, M. Marsch, A. Geyer. Stereoselective synthesis of highly functionalized thiopeptide thiazole fragments from uronic acid/cysteine condensation products: access to the core dipeptide of the thiazomycins and nocathiacins. Tetrahedron 2012, 68, 7166-7178.
R. Wieneke, A. Bernecker, R. Riedel, M. Sumper, C. Steinem, A. Geyer. Silica precipitation with synthetic silaffin peptides. Org. Biomol. Chem. 2011, 9, 5482-5486.
O. Dehus, M. Pfitzenmaier, G. Stuebs, N. Fischer W. Schwaeble, S. Morath, T. Hartung, A. Geyer, C. Hermann. Growth temperature-dependent expression of structural variants of Listeria monocytogenes lipoteichoic acid. Immunobiology 2011, 216, 24-31.
