PolyPeptide Group (United States)

For decades, chemists have followed Nature's lead, developing methods to make peptides in water. For the aqueous variant of the ubiquitous solid-phase peptide synthesis (ASPPS) in particular, significant advances have been reported, albeit with scope restricted to simple linear peptides. We report the aqueous removal of a p-nitrobenzyloxycarbonyl (pNZ) amino protecting group (PG) as an entry to the ASPPS of ε-Lys branched peptides. Using this new ASPPS approach, a bis-ε-Lys-amino acid (AA)-functionalized peptide resin was obtained, which upon FeCl3/AcOH cleavage furnished a bis-ε-Lys peptide in a manner comparable to cleavage with the standard reagent TFA. This result demonstrates compatibility of ASPPS of complex peptides with PFAS-free resin cleavage, opening a new area within the realms of sustainable peptide synthesis.

Universal Fmoc/t-Bu solid-phase peptide synthesis (SPPS) has long been intertwined with harmful substances such as dimethylformamide (DMF) and PFAS-classified trifluoroacetic acid (TFA). Having eliminated DMF and TFA from peptide synthesis by aqueous SPPS (ASPPS) [Pawlas, J.; Rasmussen, J. H. Circular Aqueous Fmoc/t-Bu Solid-Phase Peptide Synthesis. ChemSusChem 2021, 14, 3231-3236] and Brønsted acid-Lewis acid-induced resin cleavage [Pawlas, J.; André, C.; Rasmussen, J. H.; Ludemann-Hombourger, O. Brønsted Acid-Lewis Acid (BA-LA) Induced Final Deprotection/Peptide Resin Cleavage in Fmoc/t-Bu Solid-Phase Peptide Synthesis: HCl/FeCl3 and AcOH/FeCl3 as Viable PFAS-Free Alternatives for TFA. Org. Lett. 2024, 26, 6787-6791], we now report that ASPPS can be integrated with disulfide formation and TFA/PFA-free cleavage toward a new platform for sustainable synthesis of cyclic peptides, illustrated by synthesizing labor suppressant atosiban by both on-resin cyclization/cleavage and cleavage/solution cyclization approaches.

A historical sketch of the development of plastic pipe production in the Russian Federation is presented. The data on the production of pressure pipes of large diameter up to 1600 mm, non-pressure pipes for sewage, with a diameter of up to 2.5 m, pressure reinforced pipes based on cross-linked polyethylene and thermoplastics are presented. The trends in the development of the production of various types of pipes are characterized and data on the specifi cs of their application are given. The technological features of enterprises are analyzed, highlighting the preferred categories of pipes produced by the enterprises in the highest quality categories.

A cost and synthetic efficient method that enables facile reagent and solvent recycling in SPPS using cross-linked polystyrene resins in greener solvents is reported.

Solubility data were measured for N-chloro succinimide in pure n-butanol, ethyl acetate, acetone, isopropanol, tetrahydrofuran, acetonitrile and acetic anhydride at the temperature range between 278.15 K and 333.15 K under atmospheric pressure by gravimetric method. The solubility of N-chloro succinimide in those selected solvents increased with increasing temperature. The solubility data were correlated with the modified Apelblat equation and the van’t Hoff equation to obtain the model parameters. The experimental results could be useful for optimizing the process of purification of N-chloro succinimide in industry. Isopropanol could be the excellent solvent in the crystallization of N-chloro succinimide.

Josephson transport through a single molecule or carbon nanotube is considered in the presence of a local vibrational mode coupled to the electronic charge. The ground-state solution is obtained exactly in the limit of a large superconducting gap, and is extended to the general case by variational analysis. Coherent charge fluctuations are entangled with non-classical phonon states. The Josephson current induces squeezing of the phonon mode, which is controlled by the superconducting phase difference and by the junction asymmetry. Optical probes of non-classical phonon states are briefly discussed.

The combination of a long-acting delivery system for the agonist [D-Trp6]luteinizing hormone-releasing hormone ([D-Trp6]LH-RH) with modern somatostatin analogs was studied in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH releasing 25 micrograms/day were injected once a month. In the first experiment the adjunct was the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), administered at a dose of 2.5 micrograms twice a day, and the therapy was continued for 70 days. Tumor volume was significantly decreased by [D-Trp6]LH-RH microcapsules or RC-121 given alone. The combination of microcapsules and analog RC-121 caused a greater inhibition of tumor growth than the single agents. Similar effects were seen when the percent increase in the tumor volume was examined. The inhibition of tumor growth caused by the [D-Trp6]LH-RH microcapsules was greater than that caused by RC-121. The combination of the two agents was again the most effective, resulting in the smallest increase in tumor volume. Tumor weights were much lower in the groups treated with microcapsules or RC-121 alone than in controls. The lowest tumor weights were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and RC-121. Similar results were obtained in the second experiment, in which the animals were treated for a period of 83 days with microcapsules containing the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) that released 5 micrograms/day and were injected twice a month alone or in combination with microcapsules of [D-Trp6]LH-RH. Microcapsules of analog RC-160 given alone significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The inhibition of tumor growth induced by [D-Trp6]LH-RH microcapsules was greater than that caused by RC-160. The most striking decrease in tumor weight and volume was obtained in animals treated with microcapsules of [D-Trp6]LH-RH combined with the delayed delivery system for RC-160. The overall response to the combination therapy could reflect the inhibition by somatostatin analogs of the proliferation of prostate cancer cells through a decrease in growth hormone and prolactin release and interference with endogenous growth factors, in addition to the main effect, which is the suppression by [D-Trp6]LH-RH of the growth of androgen-dependent tumor cells. Our results indicate that somatostatin analogs enhance the inhibitory effects of [D-Trp6]LH-RH on the growth of prostate tumors. The administration of somatostatin analogs in combination with microcapsules of [D-Trp6]LH-RH might improve clinical response in patients with advanced prostate carcinoma.

SummaryHypothalamic tissue of porcine origin was extracted with 2 N acetic acid at 8°C. The acetic acid extracts were lyophilized and re-extracted with glacial acetic acid. The material thus concentrated was subjected to gel filtration on Sephadex. Thyrotropic hormone-releasing factor (TRF) activity was followed by measuring the release of thyrotropic hormone (TSH) from rat pituitary tissue in vitro, the release of I131 in mice pretreated with codeine and thyroxine, as well as the elevation of plasma TSH in thyroidectomized rats pretreated with thyroxine. TRF activity was consistently found to emerge between the peaks of α-MSH and lysine vasopressin. Partially purified TRF of porcine origin was active in vitro at the dose of 20 μg and in vivo at the level of 100 μg.