The acid-base titration of bleomycin-A2 in D2O solution at 35 +/- 5 degrees has been monitored by 13C n.m.r. spectroscopy at 67.89 MHz. The following pKDa values were obtained: 3.68 +/- 0.05 (secondary amine), 5.29 +/- 0.03 (imidazole), and 8.23 +/- 0.19 (primary amine), where KDa is the dissociation constant in D2O solution. The equilibrium isotope effects (pKDa--pKa in H2O) are: 0.70 +/- 0.06 (secondary amine), 0.28 +/- 0.04 (imidazole), and 0.85 +/- 0.19 (primary amine). Titration of the imidazole group of Bleo-A2 occurs at Npi, i.e. only Ntau is protonated in basic solution. Significant protonation shifts are almost completely limited to carbons of the N-terminal tetrapeptide, suggesting that the C-terminal tripeptide extends into the solvent and interacts to a minimal extent with the rest of the molecule. Long range protonation shifts associated with titration of the imidazole and secondary amine groups indicate that protonation of one or both of these sites is probably accompanied by significant conformational changes. The observed protonation shifts generally fail to correlate with Zn(II) complexation shifts reported by Dabrowiak et al. (1973, Biochemistry 17., 4090) indicating that ligation sites cannot unambiguously be determined from these complexation shifts. The complexation shifts previously attributed to coordination of the imidazole and carbamoyl groups probably result from conformational changes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1399-3011.1980.tb02913.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
mHealth Incentivized Adherence Plus Patient Navigation (MIAPP): protocol for a pilot randomized controlled trial to improve linkage and retention on buprenorphine for hospitalized patients with methamphetamine use and opioid use disorder.
Addict Sci Clin Pract
January 2025
Department of Medicine, Division of General Internal Medicine, University of Washington/Harborview Medical Center, 325 9Th Avenue, Box 359780, Seattle, WA, 98104, USA.
Background: Initiation of buprenorphine for treatment of opioid use disorder (OUD) in acute care settings improves access and outcomes, however patients who use methamphetamine are less likely to link to ongoing treatment. We describe the intervention and design from a pilot randomized controlled trial of an intervention to increase linkage to and retention in outpatient buprenorphine services for patients with OUD and methamphetamine use who initiate buprenorphine in the hospital.
Methods: The study is a two-arm pilot randomized controlled trial (N = 40) comparing the mHealth Incentivized Adherence Plus Patient Navigation (MIAPP) intervention to treatment as usual.
Cleaning and sterilization are critical Prerequisite Programs in sanitation management based on HACCP. Most food factories clean and sanitize equipment daily after production using detergents containing benzalkonium chloride (BAC). However, in factories that produce oil and fat-rich foods, it has been discovered that microbes can persist on production equipment.
View Article and Find Full Text PDFTriethylamine-mediated protonation-deprotonation unlocks dual-drug self assembly to suppress breast cancer progression and metastasis.
Proc Natl Acad Sci U S A
February 2025
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.
Carrier-free nanomedicines exhibited significant potential in elevating drug efficacy and safety for tumor management, yet their self assembly typically relied on chemical modifications of drugs or the incorporation of surfactants, thereby compromising the drug's inherent pharmacological activity. To address this challenge, we proposed a triethylamine (TEA)-mediated protonation-deprotonation strategy that enabled the adjustable-proportion self assembly of dual drugs without chemical modification, achieving nearly 100% drug loading capacity. Molecular dynamic simulations, supported by experiment evidence, elucidated the underlying self-assembly mechanism.
View Article and Find Full Text PDFClinical Efficacy Between Intravenous Paracetamol and Intravenous Fentanyl for Propofol Deep Sedation in Colonoscopy: A Randomized Controlled Trial.
Drug Des Devel Ther
January 2025
Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Introduction: Sedation practices for colonoscopy indeed vary widely around the globe. Due to a lack of data on intravenous paracetamol, we aimed to investigate the clinical efficacy of intravenous paracetamol compared to intravenous fentanyl under propofol deep sedation for colonoscopy.
Methods: A total of 225 patients who underwent colonoscopy at Siriraj Hospital were randomly assigned to two groups.
Effects of Elexacaftor-Tezacaftor-Ivacaftor on Nasal and Sinus Symptoms in Children With Cystic Fibrosis.
Pediatr Pulmonol
January 2025
Hôpital Femme Mère Enfant, Hospices Civils de Lyon, 59 Boulevard Pinel, Lyon, France.
Background: New CFTR Modulator triple therapy Elexacaftor-Ivacaftor-Tezacaftor (ETI) prove efficacy in pulmonary outcomes. However, its impact on nasal sinus symptoms in children has not been specifically studied. The aim of this study is to evaluate the impact of this therapy on nasal sinus symptomatology in children aged 6-12 years.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!