Dipeptidyl peptidase IV (DP IV)-catalyzed hydrolysis of the NH2-X-Pro-containing N-terminal dodecapeptide of IL-2 was studied using free zone capillary electrophoresis as an alternative peptidase assay. In contrast to the conventional DP IV substrate glycyl-prolyl-p-nitroanilide (Gly-Pro-pNA), the hydrolysis of this peptide by DP IV was found to be significantly inhibited by anti-DP IV antibodies. Inhibition of DP IV was also observed with a number of non-substrate oligopeptides containing an N-terminal X-X-Pro- structure, including the HIV Tat protein. For Met-IL-2(1-6), we determined a competitive inhibition with an inhibition constant of ca. 100 microM.
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http://dx.doi.org/10.1016/0021-9673(95)00411-f | DOI Listing |
PLoS Pathog
January 2025
Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Function-to-find domain (FIIND)-containing proteins, including NLRP1 and CARD8, are vital components of the inflammasome signaling pathway, critical for the innate immune response. These proteins exist in various forms due to autoproteolysis within the FIIND domain, resulting in full-length (FL), cleaved N-terminal (NT), and cleaved C-terminal (CT) peptides, which form autoinhibitory complexes in the steady state. However, the detailed mechanism remains elusive.
View Article and Find Full Text PDFCancer
February 2025
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Background: Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti-programmed death-1 antibody) in advanced solid tumor patients.
Methods: The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.
PeerJ
January 2025
Departamento de genética, ecologia e evolução, Laboratório de biologia integrativa, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Background: The angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are central human molecules in the SARS-CoV-2 virus-host interaction. Evidence indicates that may influence expression. This study aims to determine whether ACE1, ACE2, and TMPRSS2 mRNA expression levels, along with the ACE1 Alu 287 bp polymorphism (rs4646994), contribute to the severity and mortality of COVID-19.
View Article and Find Full Text PDFAm J Manag Care
January 2025
Ascension Borgess Hospital, 345 Naomi St, Plainwell, MI 49080. Email:
Objective: To describe the outcomes of a partnership between a drug plan and pharmacists to switch patients from brand name dipeptidyl-peptidase-4 inhibitors to the generic alogliptin.
Study Design: Single-center, retrospective chart review.
Methods: Clinical pharmacists contacted patients with primary care providers within the health system affiliated with the drug plan to facilitate the switch.
JAMA Otolaryngol Head Neck Surg
January 2025
OptumLabs, Eden Prairie, Minnesota.
Importance: The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RA) demands a better understanding of their association with thyroid cancer.
Objective: To estimate the risk of incident thyroid cancer among adults with type 2 diabetes being treated with GLP-1RA vs other common glucose-lowering medications.
Design, Setting, And Participants: This was a prespecified secondary analysis of a target trial emulation of a comparative effectiveness study using claims data for enrollees in commercial, Medicare Advantage, and Medicare fee-for-service plans across the US.
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