Self-assembly of angiotensin-converting enzyme inhibitors captopril and lisinopril and their crystal structures

DOI: 10.1021/acs.langmuir.1c01340

Authors: Valeria Castelletto (National Physical Laboratory, UK) , Jani Seitsonen (Aalto University) , Janne Ruokolainen (Aalto University) , Sarah A. Barnett (Diamond Light Source) , Callum Sandu (University of Reading) , Ian W. Hamley (Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Langmuir , VOL 16

State: Published (Approved)
Published: July 2021
Diamond Proposal Number(s): 26583

Abstract: The peptide angiotensin-converting enzyme inhibitors captopril and lisinopril are unexpectedly shown to exhibit critical aggregation concentration (CAC) behavior through measurements of surface tension, electrical conductivity, and dye probe fluorescence. These three measurements provide similar values for the CAC, and there is also evidence from circular dichroism spectroscopy for a possible conformational change in the peptides at the same concentration. Cryogenic transmission electron microscopy indicates the formation of micelle-like aggregates above the CAC, which can thus be considered a critical micelle concentration, and the formation of aggregates with a hydrodynamic radius of ∼6–7 nm is also evidenced by dynamic light scattering. We also used synchrotron radiation X-ray diffraction to determine the single-crystal structure of captopril and lisinopril. Our results improve the accuracy of previous data reported in the literature, obtained using conventional X-ray sources. We also studied the structure of aqueous solutions containing captopril or lisinopril at high concentrations. The aggregation may be driven by intermolecular interactions between the proline moiety of captopril molecules or between the phenylalanine moiety of lisinopril molecules.

Journal Keywords: Crystals; Solution chemistry; Peptides and proteins; Fluorescence; Crystal structure

Diamond Keywords: Enzymes

Subject Areas: Chemistry, Medicine


Instruments: I19-Small Molecule Single Crystal Diffraction

Added On: 26/07/2021 08:50

Documents:
acs.langmuir.1c01340.pdf

Discipline Tags:

Health & Wellbeing Chemistry Organic Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Single Crystal X-ray Diffraction (SXRD)