Polymerization of l-Tyrosine, l-Phenylalanine, and 2-Phenylethylamine as a Versatile Method of Surface Modification for Implantable Medical Devices.

Surface properties are crucial for medical device and implant research and applications. We present novel polycatecholamine coatings obtained by oxidative polymerization of l-tyrosine, l-phenylalanine, and 2-phenylethylamine based on mussel glue-inspired chemistry. We optimized the reaction parameters and examined the properties of coatings compared to the ones obtained from polydopamine. We produced polycatecholamine coatings on various materials used to manufacture implantable medical devices, such as polyurethane, but also hard-to-coat polydimethylsiloxane, polytetrafluoroethylene, and stainless steel. The coating process results in significant hydrophilization of the material's surface, reducing the water contact angle by about 50 to 80% for polytetrafluoroethylene and polyurethane, respectively. We showed that the thickness, roughness, and stability of the polycatecholamine coatings depend on the chemical structure of the oxidized phenylamine. In vitro experiments showed prominent hemocompatibility of our coatings and significant improvement of the adhesion and proliferation of human umbilical vein endothelial cells. The full confluence on the surface of coated polytetrafluoroethylene was achieved after 5 days of cell culture for all tested polycatecholamines, and it was maintained after 14 days. Hence, the use of polycatecholamine coatings can be a simple and versatile method of surface modification of medical devices intended for contact with blood or used in tissue engineering.

PSMA targeted conjugates based on dextran.

BACKGROUND: Currently, radiotherapy is one of the most popular choices in clinical practice for the treatment of cancers. While it offers a fantastic means to selectively kill cancer cells, it can come with a host of side effects. To minimize such side effects, and maximize the therapeutic effect of the treatment, we propose the use of targeted radiopharmaceuticals. In the study presented herein, we investigate two synthetic pathways of dextran-based radiocarriers and provide their key chemical and physical properties: stability of the bonding of chelating agent and tertiary structure of obtained formulations and its influence on biological properties. Additionally, PSMA small molecule inhibitor was attached and quantified using DELFIA fluorescence assay. Finally, biological properties and radiolabeling yield were studied using confocal microscopy and ITLC-SG chromatography. RESULTS: Two types of Dex-conjugates - micelle-like nanoparticles (NPs) and non-folded conjugates - were successfully generated and shown to exhibit cellular effects. The tertiary structure of the conjugates was found to influence the selectivity of PSMA and mediate cell binding as well as cellular uptake mechanisms. NPs were shown to be internalized by other, non - PSMA mediated channels. Simultaneously, the uptake of non-folded conjugates required PSMA inhibitor to pass through cell membrane. The radiochemical yield of NHS coupled DOTA chelator was between 91.3 and 97.7% while the TCT-amine bonding showed higher stability and gave the yields of 99.8-100%. CONCLUSIONS: We obtained novel, dextran-based radioconjugates, and presented a superior method of chelator binding, resulting in exquisite radiochemical properties as well as selective cross-membrane transport.

Static Combinatorial Chemistry: A High-Pressure Approach to the Synthesis of Macrocyclic Benzoamide Libraries.

We investigated the yield and distribution of macrocyclic products formed in combinatorial libraries (CLs) obtained via double-amidation reactions of methyl diesters with α,ω-diamines. The application of the static combinatorial chemistry (SCC) approach allowed us to generate a large number of macrocyclic diamides and tetraamides in single experiments. We show that high-pressure conditions accelerate the macrocyclization process but also have a great impact on the distribution of macrocyclic products in the presented libraries, promoting the formation of macrocyclic compounds and eliminating the linear ones. The distribution of macrocyclic products was also found to be strongly dependent on the structural features of the substrates employed. Furthermore, in three- and four-substrate CLs we observed the formation of a new type of hybrid tetraamides consisting of three different components.

Chiral Recognition of Carboxylate Anions by (R)-BINOL-Based Macrocyclic Receptors.

Three (R)-BINOL-based macrocyclic receptors obtained via double-amidation reaction were used for chiral recognition of four anions derived from α-hydroxy and α-amino acids. The structural factors of hosts and guests that affect chiral recognition processes were also investigated, indicating that the proper geometry of both receptor and guest molecules plays a crucial role in effective enantio-discrimination.

Late-Stage Functionalization of ( R)-BINOL-Based Diazacoronands and Their Chiral Recognition of α-Phenylethylamine Hydrochlorides.

Five BINOL-based hosts with a variable macroring size were synthesized in a two-step postfunctionalization protocol by double N-benzylation followed by BMS-mediated reduction of tertiary amide groups (53-93%). UV-vis titration in MeCN reveals that all hosts exhibit a preference for the ( R)-enantiomer over the ( S)-enantiomer of PEA-HCl. The enantioselectivity depends on the number of hydrogen bond (HB) acceptors and the size and flexibility of the macroring. The highest enantiodiscrimination was observed for the 20-membered host 10, containing six HB acceptors ( KR/ KS = 2.13).