This study uses EPR, CD, and fluorescence spectroscopy to examine the structure of bradykinin (BK) analogues attaching the paramagnetic amino acid-type Toac (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) at positions 0, 3, 7, and 9. The data were correlated with the potencies in muscle contractile experiments and the substrate properties towards the angiotensin I-converting enzyme (ACE). A study of the biological activities in guinea pig ileum and rat uterus indicated that only Toac-BK partially maintained its native biological potency among the tested peptides. This and its counterpart, Toac-BK, maintained the ability to act as ACE substrates. These results indicate that peptides bearing Toac probe far from the ACE cleavage sites were more susceptible to hydrolysis by ACE. The results also emphasize the existence of a finer control for BK-receptor interaction than for BK binding at the catalytic site of this metallodipetidase. The kinetic kcat/Km values decreased from 202.7 to 38.9μMmin for BK and Toac-BK, respectively. EPR, CD, and fluorescence experiments reveal a direct relationship between the structure and activity of these paramagnetic peptides. In contrast to the turn-folded structures of the Toac-internally labeled peptides, more extended conformations were displayed by N- or C-terminally Toac-labeled analogues. Lastly, this work supports the feasibility of monitoring the progress of the ACE-hydrolytic process of Toac-attached peptides by examining time-dependent EPR spectral variations.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.bioorg.2016.10.006 | DOI Listing |
Allergy Asthma Proc
January 2025
From the Division of Allergy and Immunology, Department of Medicine, University of California San Diego, La Jolla, California and.
Idiopathic non-mast cell angioedema (INMA) is a rare disease typified by recurrent attacks of cutaneous and subcutaneous swelling. Every attack carries the potential for severe morbidity and, in the case of laryngeal involvement, mortality. Whereas therapies approved for hereditary angioedema (HAE) have been used in the care of patients with INMA, little is known with regard to their efficacy for the treatment of this disease.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
December 2024
Department of Physiology.
Endothelial cell-selective adhesion molecule (ESAM) is a member of tight junction molecules, highly abundant in the heart and the lung, and plays a role in regulating endothelial cell permeability. We previously reported that mice with genetic ESAM deficiency (ESAM) exhibit coronary microvascular dysfunction leading to the development of left ventricular diastolic dysfunction. Here, we hypothesize that ESAM mice display impairments in the pulmonary vasculature, affecting the overall pulmonary vascular resistance (PVR).
View Article and Find Full Text PDFJ Org Chem
January 2025
Department of Radiology, Mayo Clinic, Rochester, Minnesota 55906, United States.
Conjugation of radiofluorinated prosthetic groups to primary amines of peptides in an aqueous medium is still considerably challenging. Herein, we report a one-pot cascade synthesis of 1-[F]fluoro-4-isothiocyanatobenzene ([F]), an isothiocyanate-functionalized prosthetic group for radiolabeling of various peptides in aqueous medium. The developed compound [F] was synthesized in >99% radiochemical purity with 22.
View Article and Find Full Text PDFArch Dermatol Res
December 2024
Department of Public Health, Atish Dipankar University of Science and Technology, Dhaka, Bangladesh.
Hereditary angioedema with C1 inhibitor deficiency (HAE-C1-INH) is a rare disorder characterized by recurrent, potentially life-threatening swelling in various parts of the body, including the limbs, face, and airways Current treatments focus primarily on symptomatic relief and the management of acute attacks, without targeting the underlying genetic cause or the dysregulated bradykinin production. Donidalorsen, a novel antisense oligonucleotide, addresses a key driver of HAE-C1-INH by targeting prekallikrein (PKK) to reduce bradykinin levels. This meta-analysis evaluates the efficacy and safety of Donidalorsen versus placebo, focusing on two dosing regimens: 4-week and 8-week intervals.
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2024
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 75207, USA.
Bradykinin is an endogenously produced nonapeptide with many physiological and pathological functions that are mediated by two pharmacologically defined receptor subtypes, B1- and B2-receptors. Current studies sought to characterize the functional bradykinin (BK) receptors present in freshly isolated bovine ciliary muscle (BCM) using an organ-bath tissue contraction system. Cumulative longitudinal isometric tension responses of BCM strips (4-5 mm) were recorded before and after the addition of test compounds to BCM strips hooked up to an isometric strain gauge transducer system.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!