Article
Medicine, Research & Experimental
Kai-Chia Yeh, Teng-Kuang Yeh, Chung-Yu Huang, Chih-Bo Hu, Min-Hsien Wang, Yu-Wen Huang, Ling-Hui Chou, Hsuan-Hui Ho, Jen-Shin Song, Tsu Hsu, Weir-Torn Jiaang, Yu-Sheng Chao, Chiung-Tong Chen
Summary: DBPR108 is a novel DPP-4-selective inhibitor that has demonstrated potent in vivo pharmacological effects and good safety profiles in animals. By inhibiting DPP-4 activity, it increases active GLP-1 and insulin levels while improving glucose tolerability in animals.
Review
Biochemistry & Molecular Biology
Marija Abramic, Dejan Agic
Summary: This review discusses natural and synthetic compounds with inhibitory activity towards DPP III in mammals, as well as strategies and mechanisms of inhibitory actions. Some of these inhibitors exhibit high activity at low nanomolar or low micromolar concentrations. The review also introduces oligopeptides from the hemorphin group and transition-state peptidomimetics inhibitors as potential DPP III inhibitors.
Article
Biochemistry & Molecular Biology
Zrinka Karacic, Filip Supljika, Antonija Tomic, Lidija Brkljacic, Ana Tomasic Paic, Mirsada Cehic, Sanja Tomic
Summary: Dipeptidyl peptidase III (DPP III) is an enzyme involved in protein degradation and plays important roles in blood pressure regulation and pain regulation. We investigated various neuropeptides as potential substrates and inhibitors of DPP III, and identified several potent inhibitors and a highly effective substrate. The computational analysis provided insights into the differences between substrates that are hydrolyzed effectively and those hydrolyzed slowly by DPP III.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Food Science & Technology
Juan Wang, Yujia Xie, Yuanyuan Luan, Tingting Guo, Shanshan Xiao, Xingxing Zeng, Shaohui Zhang
Summary: The objective of this study was to isolate and identify intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide (LPS) stimulation. A total of 131 novel peptides were discovered, and their bioactivity and function were predicted. Two peptides with better inhibition activity were verified.
FOOD SCIENCE AND HUMAN WELLNESS
(2022)
Article
Nutrition & Dietetics
Paulina Keska, Joanna Stadnik
Summary: This study found that peptides extracted from dry-cured pork loins have inhibitory effects on dipeptidyl peptidase IV, and retain their biological activity during the digestive process. These peptides may have potential as functional food ingredients for preventing and treating type 2 diabetes mellitus. Certain peptide sequences show promise as natural food compounds for maintaining good health.
Article
Endocrinology & Metabolism
Linong Ji, Jinmiao Lu, Leili Gao, Changjiang Ying, Jiao Sun, Jie Han, Wenhua Zhao, Yunming Gao, Kun Wang, Xin Zheng, Daosheng Xie, Juping Ding, Jiahong Zhao, Qiang Yu, Tong Wang
Summary: This study assessed the efficacy and safety of the dipeptidyl peptidase-4 inhibitor, cetagliptin, as monotherapy in Chinese patients with type 2 diabetes (T2D). The results showed that cetagliptin effectively reduced HbA1c levels, and the incidence of adverse events was similar to the placebo group. Therefore, cetagliptin monotherapy is effective and well tolerated in Chinese patients with T2D.
DIABETES OBESITY & METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Ankit Gupta, Hayder A. Al-Aubaidy, Christian K. Narkowicz, Herbert F. Jelinek, David S. Nichols, John R. Burgess, Glenn A. Jacobson
Summary: Citrus bioflavonoids are plant-derived pigments with powerful antioxidant and cardioprotective effects. The study reveals variations in citrus bioflavonoid content and DPP-4 inhibitory potential among commercially available supplements.
Article
Endocrinology & Metabolism
Linong Ji, Jinmiao Lu, Leili Gao, Xiaoguang Yan, Jifang Li, Zhifeng Cheng, Lili Zhang, Junhang Tian, Ping Li, Jie Bai, Daosheng Xie, Jiahong Zhao, Juping Ding, Qiang Yu, Tong Wang
Summary: This study aimed to evaluate the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes. The results showed that the addition of cetagliptin was more effective in glycemic control and well tolerated compared to metformin monotherapy.
DIABETES OBESITY & METABOLISM
(2023)
Article
Agriculture, Dairy & Animal Science
Priti Mudgil, Ali Ali Redha, Nilesh P. Nirmal, Sajid Maqsood
Summary: Milk protein hydrolysates from different camel breeds showed significant variations in inhibitory effects on antidiabetic and antihypercholesterolemic enzymes, with higher inhibition observed in Hozami and Omani camel breeds. In vitro simulated digestion processes enhanced the bioactive properties of milk from all camel breeds. Breed selection is important for the production of bioactive peptides.
JOURNAL OF DAIRY SCIENCE
(2023)
Article
Ophthalmology
Masaaki Yoshida, Taiki Kokubun, Kota Sato, Satoru Tsuda, Yu Yokoyama, Noriko Himori, Toru Nakazawa
Summary: This study investigated the effect of DPP-4 inhibitors on fibrosis after glaucoma filtering surgery. The results showed that DPP-4 inhibitors increased the survival rate of blebs in patients with diabetes and NVG. In vitro experiments demonstrated that linagliptin attenuated fibrotic change in HTFs by inhibiting TGF-β3/Smad signaling.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Chao Lin, Ying Kong, Furong Wang, Rong Rong, Xiangping Li, Rensong Xiao, Ziqi Wu, Qiuyan Zhang, Lin Wang
Summary: In this study, a series of new DPP-4 inhibitors were designed and synthesized, and compound 6c showed promising potential for the treatment of T2DM with better pharmacokinetic profile and efficacy.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Dejan Agic, Maja Karnas, Sanja Tomic, Mario Komar, Zrinka Karacic, Vesna Rastija, Drago Beslo, Domagoj Subaric, Maja Molnar
Summary: This study investigated the inhibitory activity of 27 quinazolinone-Schiff's bases against human DPP III and identified five most potent inhibitors. These compounds were found to bind to the central enzyme cleft and interact with residues of the substrate binding subsites to exert inhibitory effects. Additionally, molecular dynamics simulations provided valuable insights into the mechanism of inhibitor binding and stabilization.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Hugo Ramos, Patricia Bogdanov, Jordi Huerta, Anna Deas-Just, Cristina Hernandez, Rafael Simo
Summary: Sitagliptin eye drops have antioxidant and anti-inflammatory effects on the diabetic retina, reducing oxidative stress, protecting against DNA/RNA/protein damage, and preventing downregulation of antioxidant enzymes.
Article
Endocrinology & Metabolism
Mona Mashayekhi, Jessica R. Wilson, Scott Jafarian-Kerman, Hui Nian, Chang Yu, Megan M. Shuey, James M. Luther, Nancy J. Brown
Summary: Genetic variation in the gene encoding the GLP-1 receptor may affect the metabolic response to DPP-4 inhibitors. The rs6923761 variant was associated with decreased postprandial glucose excursion in individuals with type 2 diabetes and hypertension. The study suggests a potential role of GLP1R rs6923761 genotype in modulating GLP-1 signaling in response to treatment.
DIABETES OBESITY & METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Antonia Matic, Filip Supljika, Hrvoje Brkic, Jasna Jurasovic, Zrinka Karacic, Sanja Tomic
Summary: DPP III is a monozinc metalloexopeptidase that hydrolyzes dipeptides and plays a role in the regulation of various physiological processes. We conducted studies to understand the binding and exchange of physiologically relevant metal ions in DPP III. Our results showed different affinities for Zn2+, Cu2+, and Co2+ in the catalytic and additional binding sites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sara Matic, Ivana Kekez, Marko Tomin, Ferenc Bogar, Filip Supljika, Sasa Kazazic, Maja Hanic, Shalinee Jha, Hrvoje Brkic, Benjamin Bourgeois, Tobias Madl, Karl Gruber, Peter Macheroux, Dubravka Matkovic-Calogovic, Mihaela Matovina, Sanja Tomic
Summary: This study highlights the synergy between theory and experiment in elucidating the binding mechanism between DPP III and KEAP1, shedding light on the significance of the NRF2-KEAP1 signaling pathway in antioxidant stress response.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Multidisciplinary
Matthias Ferger, Zeljka Ban, Ivona Krosl, Sanja Tomic, Lena Dietrich, Sabine Lorenzen, Florian Rauch, Daniel Sieh, Alexandra Friedrich, Stefanie Griesbeck, Adriana Kendel, Snezana Miljanic, Ivo Piantanida, Todd B. Marder
Summary: The new luminescent tetracationic bis-triarylborane DNA and RNA sensors exhibit high binding affinities, with substituted bis(2,6-dimethylphenyl-4-ethynyl)arene linkers serving as efficient dual Raman and fluorescence chromophores. The linker length and flexibility significantly affect the binding affinities, with triple bonds playing a crucial role in Raman activity. The insertion of aromatic moieties between two carbon-carbon triple bonds offers an alternative design for dual Raman and fluorescence chromophores in biological imaging applications.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Medicinal
Borka Loncar, Natasa Perin, Marija Mioc, Ida Bocek, Lea Grgic, Marijeta Kralj, Sanja Tomic, Marijana Radic Stojkovic, Marijana Hranjec
Summary: A novel series of tetracyclic imidazo[4,5-b]pyridine derivatives were designed and synthesized as potential antiproliferative agents, with the position of N atom in the pyridine nuclei significantly impacting their activity against human cancer cells. Some compounds showed improved activity compared to standard drug etoposide, particularly on HCT116 and MCF-7 cancer cells. The position of N nitrogen in the pyridine ring and the presence of amino side chains on the tetracyclic core influenced interactions with DNA/RNA and the enhancement of antiproliferative activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Zeljka Ban, Zrinka Karacic, Sanja Tomic, Hashem Amini, Todd B. Marder, Ivo Piantanida
Summary: Novel dyes were prepared by simple click CuAAC attachment, which interact specifically with proteins while their affinity to DNA/RNA is completely abolished. These dyes exhibit strong fluorescence enhancement upon binding to proteins, and the triarylborane-pyrene conjugate retains FRET effect when binding to the hDPP III enzyme.
Article
Multidisciplinary Sciences
Diana Trnski, Maja Sabol, Sanja Tomic, Ivan Stefanac, Milanka Mrcela, Vesna Musani, Nikolina Rincic, Matea Kurtovic, Tina Petric, Sonja Levanat, Petar Ozretic
Summary: Prostate cancer is the second most frequent cancer in men worldwide, with different treatment strategies for localized versus advanced cases. Research suggests that the Hedgehog-GLI signaling pathway plays a crucial role in sustaining androgen-independent growth of prostate cancer cells.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Sara Matic, Ana Tomasic Paic, Sandra Sobocanec, Marija Pinteric, Goran Pipalovic, Monika Martincic, Mihaela Matovina, Sanja Tomic
Summary: The DPP III-R623W variant has higher affinity for KEAP1 and upregulates NQO1 expression, thus activating the KEAP1-NRF2 pathway. These findings provide new insight into the involvement of DPP III in cancer progression and prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Antonija Tomic, Sanja Tomic
Summary: In this study, we investigate the catalytic cycle of human DPP III and provide theoretical insights into the inhibitory mechanism of tynorphin. Our findings reveal that tynorphin is cleaved by the same mechanism as Leu-enkephalin, and the stabilization of the product and regeneration of the enzyme are the rate-determining steps of the overall catalytic cycle.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Iva Zonjic, Lidija-Marija Tumir, Ivo Crnolatac, Filip Supljika, Livio Racane, Sanja Tomic, Marijana Radic Stojkovic
Summary: Interactions between a series of benzothiazole ligands and nucleic acid structures were screened using competition dialysis. Two compounds demonstrated high affinities against 13 nucleic acid structures, while another compound showed high selectivity among the studied compounds. Additionally, some compounds exhibited specific effects on certain nucleic acid structures.
Article
Biochemistry & Molecular Biology
Zrinka Karacic, Filip Supljika, Antonija Tomic, Lidija Brkljacic, Ana Tomasic Paic, Mirsada Cehic, Sanja Tomic
Summary: Dipeptidyl peptidase III (DPP III) is an enzyme involved in protein degradation and plays important roles in blood pressure regulation and pain regulation. We investigated various neuropeptides as potential substrates and inhibitors of DPP III, and identified several potent inhibitors and a highly effective substrate. The computational analysis provided insights into the differences between substrates that are hydrolyzed effectively and those hydrolyzed slowly by DPP III.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Dejan Agic, Maja Karnas, Sanja Tomic, Mario Komar, Zrinka Karacic, Vesna Rastija, Drago Beslo, Domagoj Subaric, Maja Molnar
Summary: This study investigated the inhibitory activity of 27 quinazolinone-Schiff's bases against human DPP III and identified five most potent inhibitors. These compounds were found to bind to the central enzyme cleft and interact with residues of the substrate binding subsites to exert inhibitory effects. Additionally, molecular dynamics simulations provided valuable insights into the mechanism of inhibitor binding and stabilization.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Antonija Tomic, Zrinka Karacic, Sanja Tomic
Summary: Dipeptidyl peptidase III (DPP III), a zinc exopeptidase, plays a role in intercellular protein degradation and shows affinity for opioid peptides. Mutations in R399 and R669 affect the binding and inhibitory properties of different neuropeptides towards DPP III. The R669A mutation decreases the inhibitory potency of slow substrates, while the R399A mutation affects both good and slow substrates, especially Leu-enkephalin.
Article
Biochemistry & Molecular Biology
Mihaela Matovina, Ana Tomasic Paic, Sanja Tomic, Hrvoje Brkic, Lucija Horvat, Lea Barbaric, Vedrana Filic, Marija Pinteric, Snjezana Juric, Akmaral Kussayeva
Summary: DPP3 is a zinc-dependent exopeptidase that regulates the oxidative stress response pathway through interaction with KEAP1. We have identified SH2D3C as an interacting protein of DPP3 and demonstrated their colocalization and direct interaction in cells. This interaction suggests that DPP3 and SH2D3C may play a role in cell adhesion, migration, and immune response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Antonia Matic, Filip Supljika, Hrvoje Brkic, Jasna Jurasovic, Zrinka Karacic, Sanja Tomic
Summary: DPP III is a monozinc metalloexopeptidase that hydrolyzes dipeptides and plays a role in the regulation of various physiological processes. We conducted studies to understand the binding and exchange of physiologically relevant metal ions in DPP III. Our results showed different affinities for Zn2+, Cu2+, and Co2+ in the catalytic and additional binding sites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
S. Matic, I. Kekez, M. Hanic, F. Supljika, M. Matovina, S. Tomic
Article
Chemistry, Physical
Antonija Tomic, Hrvoje Brkic, Antonia Matic, Sanja Tomic
Summary: DPP III is widely distributed in human tissues and plays roles in protein catabolism, oxidative stress, blood pressure regulation, and pain modulation. Excess zinc ions can inhibit its hydrolytic activity, and the study determined the inhibitory zinc ion binding site using computational approaches.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)