Models of binding of 4′-nitrophenyl α-d-mannopyranoside to the lectin concanavalin A

Molecular models for the complex formed between the lectin concanavalin A (Con A) and the saccharide derivative 4′-nitrophenyl-α-d-mannopyranoside (α-PNM) are presented, combining evidence from 1H-n.m.r. measurements, semi-empirical energy calculations and interactive graphics modelling. The models are in good agreement with the experimental data. Close examination of the models suggests that hydrophobic interactions together with van der Waals interactions and hydrogen bonds contribute to the stability of the complexes. It appears that there is a limited number of possible modes of binding of α-PNM to Con A. © 1989

On the molecular basis of the recognition of angiotensin II (AII) : NMR structure of AII in solution compared with the X-ray structure of AII bound to the mAb Fab131

The high-resolution 3D structure of the octapeptide hormone angiotensin II (AII) in aqueous solution has been obtained by simulated annealing calculations, using high-resolution NMR-derived restraints. After final refinement in explicit water, a family of 13 structures was obtained with a backbone RMSD of 0.73 ± 0.23 Å. AII adopts a fairly compact folded structure, with its C-terminus and N-terminus approaching to within ≈ 7.2 Å of each other. The side chains of Arg2, Tyr4, Ile5 and His6 are oriented on one side of a plane defined by the peptide backbone, and the Val3 and Pro7 are pointing in opposite directions. The stabilization of the folded conformation can be explained by the stacking of the Val3 side chain with the Pro7 ring and by a hydrophobic cluster formed by the Tyr4, Ile5 and His6 side chains. Comparison between the NMR-derived structure of AII in aqueous solution and the refined crystal structure of the complex of AII with a high-affinity mAb (Fab131) [Garcia, K.C., Ronco, P.M., Verroust, P.J., Brunger, A.T., Amzel, L.M. (1992) Science257, 502–507] provides important quantitative information on two common structural features: (a) a U-shaped structure of the Tyr4-Ile5-His6-Pro7 sequence, which is the most immunogenic epitope of the peptide, with the Asp1 side chain oriented towards the interior of the turn approaching the C-terminus; (b) an Asx-turn-like motif with the side chain aspartate carboxyl group hydrogen-bonded to the main chain NH group of Arg2. It can be concluded that small rearrangements of the epitope 4–7 in the solution structure of AII are required by a mean value of 0.76 ± 0.03 Å for structure alignment and ≈ 1.27 ± 0.02 Å for sequence alignment with the X-ray structure of AII bound to the mAb Fab131. These data are interpreted in terms of a biological 'nucleus' conformation of the hormone in solution, which requires a limited number of structural rearrangements for receptor–antigen recognition and binding

Thermodynamic origin of cis/trans isomers of a proline-containing beta-turn model dipeptide in aqueous solution: A combined variable temperature H-1-NMR, two-dimensional H-1,H-1 gradient enhanced nuclear Overhauser effect spectroscopy (NOESY), one-dimensional steady-state intermolecular C-13,H-1 NOE, and molecular dynamics study

Journal URL: http://www3.interscience.wiley.com/journal/28380/home?CRETRY=1&SRETRY=

Oral sucrosomial iron improves exercise capacity and quality of life in heart failure with reduced ejection fraction and iron deficiency: a non-randomized, open-label, proof-of-concept study

Aims: Oral sucrosomial iron (SI) combines enhanced bioavailability and tolerance compared to conventional oral iron along with similar efficacy compared to intravenous iron in several conditions associated with iron deficiency (ID). Methods and results: In this non-randomized, open-label study, we sought to evaluate prospectively the effects of SI on clinical parameters, exercise capacity and quality of life in 25 patients with heart failure (HF) with reduced ejection fraction (HFrEF) and ID, treated with SI 28 mg daily for 3 months, in comparison to 25 matched HFrEF controls. All patients were on optimal stable HF therapy. Patients were followed for 6 months for death or worsening HF episodes. There were no differences in baseline characteristics between groups. At 3 months, SI was associated with a significant increase in haemoglobin, serum iron and serum ferritin levels (all P ≤ 0.001) along with a significant improvement in 6-min walked distance and Kansas City Cardiomyopathy Questionnaire (all P < 0.01), even after adjustment for baseline parameters; these differences persisted at 6 months. Over the study period, there were no deaths, while 10 patients (20%) in total (four in the SI group and six in the control group), experienced worsening HF (odds ratio 0.51, 95% confidence interval 0.41–6.79, P = 0.482). Drug-associated diarrhoea was reported by one patient in the SI group and led to drug discontinuation; no other adverse events were reported. Conclusions: In this proof-of-concept study, SI was well tolerated and improved exercise capacity and quality of life in HFrEF patients with ID. Randomized studies are required to further investigate the effects of this therapy. © 2021 European Society of Cardiolog