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https://www.readbyqxmd.com/read/29773064/the-hydrocarbon-staple-beyond-recent-advances-towards-stapled-peptide-therapeutics-that-target-protein-protein-interactions
#1
Robert A Hillman, Jonathan W Nadraws, Michael A Bertucci
Anomalous protein-protein interactions (PPIs) have been correlated to a variety of disease states, such as cancer, infectious disease, neurological disorders, diabetes, endocrine disorders and cardiovascular disease. Stapled peptides are an emerging intervention for these PPIs due to their improved structural rigidity and pharmacokinetic properties relative to unstapled peptides. This review details the most recent advances in the field of stapled peptide therapeutics, including the increasing variety of PPIs being targeted and types of peptide staples being employed...
May 17, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29773063/conversion-of-protein-active-regions-into-peptidomimetic-therapeutic-leads-using-backbone-cyclization-and-cycloscan-how-to-do-it-yourself
#2
Samuel J S Rubin, Yftah Tal-Gan, Chaim Gilon, Nir Qvit
Protein-protein interactions (PPIs) are particularly important for controlling both physiologic and pathologic biological processes but are difficult to target due to their large and/or shallow interaction surfaces unsuitable for small molecules. Linear peptides found in nature interact with some PPIs, and protein active regions can be used to design synthetic peptide compounds for inhibition of PPIs. However, linear peptides are limited therapeutically by poor metabolic and conformational stability, which can compromise their bioactivity and half-life...
May 17, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29772403/theoretical-study-of-the-intermolecular-recognition-mechanism-between-survivin-and-substrate-based-on-conserved-binding-mode-analysis
#3
Chao Wu, Liguang Mao, Xie Huang, Weitao Fu, Xiong Cai, Yuepiao Cai, Liqun Shen, Xiaoxia Ye
Survivin is the smallest member of IAP (inhibitor of apoptosis protein) family, which plays important roles in both mitosis and apoptosis. It has become an attractive drug target due to its overexpression in many human cancers. Survivin has been proven to bind to Smac/DIABLO protein that indirectly inhibits apoptosis. Meanwhile, it is the key subunit of chromosome passenger complex (CPC) which bind to the N-terminal tail of phosphorylated histone H3T3ph during mitosis. Up to now, Survivin directly targeting inhibitor has yet to merge since the difficulty of disrupting the protein-protein interactions (PPIs) between Survivin and its substrate proteins...
May 8, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29770171/risk-of-gastric-cancer-development-after-eradication-of-helicobacter-pylori
#4
REVIEW
Ka-Shing Cheung, Wai K Leung
Helicobacter pylori ( H. pylori ) infection is the most important risk factor for gastric cancer (GC) development through the Correa's gastric carcinogenesis cascade. However, H. pylori eradication alone does not eliminate GC, as pre-neoplastic lesions (atrophic gastritis, intestinal metaplasia and dysplasia) may have already developed in some patients. It is therefore necessary to identify patients at high-risk for gastric cancer after H. pylori eradication to streamline the management plan. If the patients have not undergone endoscopy with histologic assessment, the identification of certain clinical risk factors and non-invasive testing (serum pepsinogen) can predict the risk of atrophic gastritis...
May 15, 2018: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29767318/strategies-for-effective-discontinuation-of-proton-pump-inhibitors
#5
REVIEW
Judith Kim, John W Blackett, Daniela Jodorkovsky
PURPOSE OF REVIEW: Proton pump inhibitors (PPIs) are effective for many conditions but are often overprescribed. Recent concerns about long-term risks have made patients re-evaluate their need to take PPIs chronically, though these population-based studies have methodological weaknesses. The goal of this review is to provide evidenced-based strategies for discontinuation of PPI therapy. RECENT FINDINGS: Given that some patients experience rebound symptoms when abruptly stopping continuous PPI therapy due to its effect on hypergastrinemia, strategies focus on avoiding rebound...
May 16, 2018: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/29766521/current-and-future-perspectives-in-the-management-of-gastroesophageal-reflux-disease
#6
REVIEW
Junichi Akiyama, Shiko Kuribayashi, Myong Ki Baeg, Nicola de Bortoli, Elen Valitova, Edoardo V Savarino, Motoyasu Kusano, George Triadafilopoulos
Although the prevalence of gastroesophageal reflux disease (GERD) used to be lower in East Asia as compared to Western countries, it has recently been increasing, most likely due to the socioeconomic development in the East. The prevalence of both GERD and functional gastrointestinal disorders (FGIDs) ranges between 10% and 25% worldwide and there are distinct subgroups of patients with overlapping of GERD and FGIDs. However, the true prevalence of an overlap between GERD and FGIDs can be determined only when a formal pathophysiological evaluation has been performed...
May 16, 2018: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29765253/use-of-histamine-h-2-receptor-antagonists-and-outcomes-in-patients-with-heart-failure-a-nationwide-population-based-cohort-study
#7
Kasper Adelborg, Jens Sundbøll, Morten Schmidt, Hans Erik Bøtker, Noel S Weiss, Lars Pedersen, Henrik Toft Sørensen
Background: Histamine H2 receptor activation promotes cardiac fibrosis and apoptosis in mice. However, the potential effectiveness of histamine H2 receptor antagonists (H2RAs) in humans with heart failure is largely unknown. We examined the association between H2RA initiation and all-cause mortality among patients with heart failure. Methods: Using Danish medical registries, we conducted a nationwide population-based active-comparator cohort study of new users of H2RAs and proton pump inhibitors (PPIs) after first-time hospitalization for heart failure during the period 1995-2014...
2018: Clinical Epidemiology
https://www.readbyqxmd.com/read/29756023/endoscopic-polymer-injection-and-endoluminal-plication-in-treatment-of-gastroesophageal-reflux-disease-evaluation-of-long-term-results
#8
Eduardo Guimarães Hourneaux De Moura, Rubens A A Sallum, Ary Nasi, Martin Coronel, Diogo Turiani Hourneaux De Moura, Eduardo Turiani Hourneaux De Moura, Mauricio Kazuyoshi Minata, Marcelo Cury, Angela Falcão, Ivan Cecconello, Paulo Sakai
Background and study aims:  Us of proton pump inhibitors (PPIs) has made endoscopic treatment of gastroesophageal reflux disease (GERD) more efficient, with reduction in morbidity and complications. However, some patients persist with symptoms despite medical treatment and some are not compliant with it or cannot afford it for financial reasons, and thus they require non-pharmacological therapeutic options such as surgical fundoplication. Surgery may be effective in the short term, but there is related morbidity and concern about its long-term efficacy...
May 2018: Endoscopy International Open
https://www.readbyqxmd.com/read/29755512/proton-pump-inhibitors-and-dementia-physiopathological-mechanisms-and-clinical-consequences
#9
REVIEW
Gloria Ortiz-Guerrero, Diana Amador-Muñoz, Carlos Alberto Calderón-Ospina, Daniel López-Fuentes, Mauricio Orlando Nava Mesa
Alzheimer's disease (AD) is the most common type of dementia, mainly encompassing cognitive decline in subjects aged ≥65 years. Further, AD is characterized by selective synaptic and neuronal degeneration, vascular dysfunction, and two histopathological features: extracellular amyloid plaques composed of amyloid beta peptide (A β ) and neurofibrillary tangles formed by hyperphosphorylated tau protein. Dementia and AD are chronic neurodegenerative conditions with a complex physiopathology involving both genetic and environmental factors...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29754277/proton-pump-inhibitor-use-h-2-receptor-antagonist-use-and-risk-of-incident-clinical-vertebral-fracture-in-women
#10
Julie M Paik, Harold N Rosen, Catherine M Gordon, Gary C Curhan
The few prospective studies examining the relation between proton pump inhibitor (PPI) use and risk of vertebral fracture (VF) suggest a higher risk, but the magnitude of the association has been inconsistent. Moreover, no prospective studies have examined the association between substantially longer duration of PPI use and VF risk. Our objective was to determine the association between PPI use, H2 RA use, and incident clinical VF in women. We conducted a prospective study in 55,545 women participating in the Nurses' Health Study...
May 12, 2018: Calcified Tissue International
https://www.readbyqxmd.com/read/29752270/the-discovery-of-two-native-baeyer-villiger-monooxygenases-for-asymmetric-synthesis-of-bulky-chiral-sulfoxides
#11
Yan Zhang, Feng Liu, Na Xu, Yin-Qi Wu, Yu-Cong Zheng, Qian Zhao, Guoqiang Lin, Hui-Lei Yu, Jian-He Xu
Two Baeyer-Villiger monooxygenases (BVMOs) designated Bo BVMO and Am BVMO were discovered from Bradyrhizobium oligotrophicum and Aeromicrobium marinum , respectively. Both monooxygenases displayed novel features for catalyzing the asymmetric sulfoxidation of bulky and pharmaceutically relevant thioethers. Evolutionary relationship and sequence analysis revealed that the two BVMOs belong to the family of typical type I BVMO and the subtype ethionamide monooxygenase. Both BVMOs are active toward medium- and long-chain aliphatic ketones as well as various thioether substrates, but ineffective toward cyclohexanone, aromatic ketones and other typical BVMO substrates...
May 11, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29751636/design-synthesis-and-evaluation-of-novel-immunomodulatory-small-molecules-targeting-the-cd40%C3%A2-cd154-costimulatory-protein-protein-interaction
#12
Damir Bojadzic, Jinshui Chen, Oscar Alcazar, Peter Buchwald
We report the design, synthesis, and testing of novel small-molecule compounds targeting the CD40⁻CD154 (CD40L) costimulatory interaction for immunomodulatory purposes. This protein-protein interaction (PPI) is a TNF-superfamily (TNFSF) costimulatory interaction that is an important therapeutic target since it plays crucial roles in the activation of T cell responses, and there is resurgent interest in its modulation with several biologics in development. However, this interaction, just as all other PPIs, is difficult to target by small molecules...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29750108/artificial-macrocycles-as-il-17a-il-17ra-antagonists
#13
Wenjia Wang, Matthew R Groves, Alexander Dömling
Interleukin 17(A) is a pro-inflammatory cytokine involved in several auto-immune and inflammatory diseases. Current antagonists against IL17(A) or its receptor (IL17R) that show efficacy in clinical trials are monoclonal-antibodies (mAbs). However, recently designed artificial macrocyles are potent IL17-IL17R antagonists. Based on Co-crystal structures, a better understanding the biological activity and SAR of the macrocycles has been elucidated, demonstrating that macrocycles can compete with mAbs for difficult targets such as PPIs...
January 1, 2018: MedChemComm
https://www.readbyqxmd.com/read/29746660/interspia-a-web-application-for-exploring-the-dynamics-of-protein-protein-interactions-among-multiple-species
#14
Daehong Kwon, Daehwan Lee, Juyeon Kim, Jongin Lee, Mikang Sim, Jaebum Kim
Proteins perform biological functions through cascading interactions with each other by forming protein complexes. As a result, interactions among proteins, called protein-protein interactions (PPIs) are not completely free from selection constraint during evolution. Therefore, the identification and analysis of PPI changes during evolution can give us new insight into the evolution of functions. Although many algorithms, databases and websites have been developed to help the study of PPIs, most of them are limited to visualize the structure and features of PPIs in a chosen single species with limited functions in the visualization perspective...
May 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29745830/megadock-web-an-integrated-database-of-high-throughput-structure-based-protein-protein-interaction-predictions
#15
Takanori Hayashi, Yuri Matsuzaki, Keisuke Yanagisawa, Masahito Ohue, Yutaka Akiyama
BACKGROUND: Protein-protein interactions (PPIs) play several roles in living cells, and computational PPI prediction is a major focus of many researchers. The three-dimensional (3D) structure and binding surface are important for the design of PPI inhibitors. Therefore, rigid body protein-protein docking calculations for two protein structures are expected to allow elucidation of PPIs different from known complexes in terms of 3D structures because known PPI information is not explicitly required...
May 8, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29741272/proton-pump-inhibitor-and-histamine-2-receptor-antagonist-use-and-risk-of-liver-cancer-in-two-population-based-studies
#16
K T Tran, Ú C McMenamin, B Hicks, P Murchie, A P Thrift, H G Coleman, L Iversen, B T Johnston, A J Lee, C R Cardwell
BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. AIMS: To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. METHODS: We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners...
May 9, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29739175/potent-potassium-competitive-acid-blockers-a-new-era-for-the-treatment-of-acid-related-diseases
#17
REVIEW
Tadayuki Oshima, Hiroto Miwa
Conventional proton pump inhibitors (PPIs) are used as a first-line therapy to treat acid-related diseases worldwide. However, they have a number of limitations including slow onset of action, influence by cytochrome P450 polymorphisms, unsatisfactory effects at night, and instability in acidic conditions. Alternative formulations of conventional PPIs have been developed to overcome these problems; however, these drugs have only introduced small advantages for controlling acid secretion compared to conventional PPIs...
May 9, 2018: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/29739099/short-term-effect-of-high-dose-pantoprazol-on-serum-and-urinary-magnesium-levels
#18
Seyit Uyar, Suleyman Dolu, Basak O Yolcular, Hamit Y Ellidag, Mehmet Kok, Feyzi Bostan, Yasin Sahinturk, Ayhan H Cekin
BACKGROUND: Proton pump inhibitor (PPI) induced hypomagnesemia is a completely unexplained issue and cases are still being reported. Long-term use is the main factor, but there are a few articles stating that it may also emerge with short-term use. We aimed to evaluate the changes of serum and urine magnesium levels during shortterm high dose pantoprazol treatment. METHODS: The serum and 24-hour urine magnesium levels of 58 patients were evaluated during the course of 2 days...
March 1, 2018: Clinical Laboratory
https://www.readbyqxmd.com/read/29731714/proton-pump-inhibitors-and-serum-magnesium-levels-in-patients-with-torsades-de-pointes
#19
Pietro E Lazzerini, Iacopo Bertolozzi, Francesco Finizola, Maurizio Acampa, Mariarita Natale, Francesca Vanni, Rosella Fulceri, Alessandra Gamberucci, Marco Rossi, Beatrice Giabbani, Michele Caselli, Ilaria Lamberti, Gabriele Cevenini, Franco Laghi-Pasini, Pier L Capecchi
Background: Torsades de pointes (TdP) is a life-threatening ventricular tachycardia occurring in long QT-syndrome patients. It usually develops when multiple QT-prolonging factors are concomitantly present, more frequently drugs and electrolyte imbalances. Since proton-pump inhibitors (PPIs)-associated hypomagnesemia is an increasingly recognized adverse event, PPIs were recently included in the list of drugs with conditional risk of TdP, despite only few cases of TdP in PPI users have been reported so far...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29730529/the-present-and-the-future-of-motif-mediated-protein-protein-interactions
#20
REVIEW
Moon-Hyeong Seo, Philip M Kim
Protein-protein interactions (PPIs) are essential to governing virtually all cellular processes. Of particular importance are the versatile motif-mediated interactions (MMIs), which are thus far underrepresented in available interaction data. This is largely due to technical difficulties inherent in the properties of MMIs, but due to the increasing recognition of the vital roles of MMIs in biology, several systematic approaches have recently been developed to detect novel MMIs. Consequently, rapidly growing numbers of motifs are being identified and pursued further for therapeutic applications...
May 3, 2018: Current Opinion in Structural Biology
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