Regionalisation of Czech hop varieties

Odrůdová skladba chmelů pěstovaných v ČR prošla v uplynulých 20 letech radikální změnou. Kromě tradiční české odrůdy, Žateckého poloraného červeňáku, se v polovině 90. let minulého století začínají pěstovat původní české hybridní odrůdy Bor, Sládek a Premiant, ke kterým po roce 2000 přibyly postupně další – Agnus, Harmonie, Rubín, Vital a Kazbek. Rajonizace je zpracována pro obsah alfa kyselin, který je determinován především přírodními podmínkami stanoviště a průběhem počasí v době vegetace. Dostatek analytických údajů pro Žatecký červeňák umožnil zpracování obsahů alfa kyselin do ročníkových rajonizačních map, ve kterých jsou v izoliniích vyznačeny mikroregiony se stejnou hladinou alfa kyselin

Cultivation of hybrid hop varieties in Czech hop growing regions

Metodika pro praxi, která řeší podmínky pěstování hybridních odrůd chmele v podmínkách chmelařských oblastí ČR. Jedná se o hybridní odrůdy Bor, Premiant, Sládek, Agnus, Harmonie a Rubín

Establishment of hop-yards by hybrids varieties

Metodika pro praxi, která řeší podmínky nutné pro zakládání chmelnic hybridními odrůdami. Jedná se o hybridní odrůdy Bor, Premiant, Sládek, Agnus, Harmonie a Rubín

Re-emerging Aspartic Protease Targets: Examining Cryptococcus neoformans Major Aspartyl Peptidase 1 as a Target for Antifungal Drug Discovery

[Image: see text] Cryptococcosis is an invasive infection that accounts for 15% of AIDS-related fatalities. Still, treating cryptococcosis remains a significant challenge due to the poor availability of effective antifungal therapies and emergence of drug resistance. Interestingly, protease inhibitor components of antiretroviral therapy regimens have shown some clinical benefits in these opportunistic infections. We investigated Major aspartyl peptidase 1 (May1), a secreted Cryptococcus neoformans protease, as a possible target for the development of drugs that act against both fungal and retroviral aspartyl proteases. Here, we describe the biochemical characterization of May1, present its high-resolution X-ray structure, and provide its substrate specificity analysis. Through combinatorial screening of 11,520 compounds, we identified a potent inhibitor of May1 and HIV protease. This dual-specificity inhibitor exhibits antifungal activity in yeast culture, low cytotoxicity, and low off-target activity against host proteases and could thus serve as a lead compound for further development of May1 and HIV protease inhibitors

Re-emerging Aspartic Protease Targets: Examining Cryptococcus neoformans Major Aspartyl Peptidase 1 as a Target for Antifungal Drug Discovery.

Cryptococcosis is an invasive infection that accounts for 15% of AIDS-related fatalities. Still, treating cryptococcosis remains a significant challenge due to the poor availability of effective antifungal therapies and emergence of drug resistance. Interestingly, protease inhibitor components of antiretroviral therapy regimens have shown some clinical benefits in these opportunistic infections. We investigated Major aspartyl peptidase 1 (May1), a secreted Cryptococcus neoformans protease, as a possible target for the development of drugs that act against both fungal and retroviral aspartyl proteases. Here, we describe the biochemical characterization of May1, present its high-resolution X-ray structure, and provide its substrate specificity analysis. Through combinatorial screening of 11,520 compounds, we identified a potent inhibitor of May1 and HIV protease. This dual-specificity inhibitor exhibits antifungal activity in yeast culture, low cytotoxicity, and low off-target activity against host proteases and could thus serve as a lead compound for further development of May1 and HIV protease inhibitors

Design, Synthesis, and Biochemical and Biological Evaluation of Novel 7‑Deazapurine Cyclic Dinucleotide Analogues as STING Receptor Agonists

Cyclic dinucleotides (CDNs) are second messengers that activate stimulator of interferon genes (STING). The cGAS-STING pathway plays a promising role in cancer immunotherapy. Here, we describe the synthesis of CDNs containing 7-substituted 7-deazapurine moiety. We used mouse cyclic GMP–AMP synthase and bacterial dinucleotide synthases for the enzymatic synthesis of CDNs. Alternatively, 7-(het)aryl 7-deazapurine CDNs were prepared by Suzuki–Miyaura cross-couplings. New CDNs were tested in biochemical and cell-based assays for their affinity to human STING. Eight CDNs showed better activity than 2′3′-cGAMP, the natural ligand of STING. The effect on cytokine and chemokine induction was also evaluated. The best activities were observed for CDNs bearing large aromatic substituents that point above the CDN molecule. We solved four X-ray structures of complexes of new CDNs with human STING. We observed π–π stacking interactions between the aromatic substituents and Tyr240 that are involved in the stabilization of CDN-STING complexes

Design, Synthesis, and Biochemical and Biological Evaluation of Novel 7‑Deazapurine Cyclic Dinucleotide Analogues as STING Receptor Agonists

Cyclic dinucleotides (CDNs) are second messengers that activate stimulator of interferon genes (STING). The cGAS-STING pathway plays a promising role in cancer immunotherapy. Here, we describe the synthesis of CDNs containing 7-substituted 7-deazapurine moiety. We used mouse cyclic GMP–AMP synthase and bacterial dinucleotide synthases for the enzymatic synthesis of CDNs. Alternatively, 7-(het)aryl 7-deazapurine CDNs were prepared by Suzuki–Miyaura cross-couplings. New CDNs were tested in biochemical and cell-based assays for their affinity to human STING. Eight CDNs showed better activity than 2′3′-cGAMP, the natural ligand of STING. The effect on cytokine and chemokine induction was also evaluated. The best activities were observed for CDNs bearing large aromatic substituents that point above the CDN molecule. We solved four X-ray structures of complexes of new CDNs with human STING. We observed π–π stacking interactions between the aromatic substituents and Tyr240 that are involved in the stabilization of CDN-STING complexes