Investigation of the binding properties between levamlodipine and HSA based on MCR-ALS and computer modeling

Levamlodipine (LEE) is a drug commonly used for antihypertensive treatment in clinical therapy. The overlapping fluorescence spectra of LEE and human serum albumin (HSA) cause some trouble in analysis of interactions between them by using the classic fluorescence method. Here, the multivariate curve resolution-alternating least squares (MCR-ALS) approach was used to overcome this disadvantage. Meanwhile, the binding properties of LEE-HSA complex were then explored through computer modeling. The MCR-ALS results suggested that LEE-HSA complex was present in the mixture solution of LEE and HSA. This conclusion was then confirmed by the Stern-Volmer equation and time-resolved fluorescence experiment. The binding constant (K-a) was 2.139 x 10(4) L.mol(-1) at 298 K. LEE was located close to the Trp-214 residue of HSA, with van der Waals forces and hydrogen bonding as main driving forces for this interaction. LEE can alter the conformation of HSA, in which the content of alpha-helix reduced from 57.2% to 52.3%. The Pi-Alkyl interactions contributed to maintaining the stability of the LEE-HSA complex. The results of molecular dynamics simulations showed that LEE-HSA complex was formed within 5 ns, and the particle size (R-g) of HSA was altered by the binding reaction. This study would promote better understanding of the transportation and distribution mechanisms of LEE in the human body. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

Levamlodipine (LEE) is commonly used for antihypertensive treatment, and its interaction with human serum albumin (HSA) was studied using multivariate curve resolution-alternating least squares (MCR-ALS) approach and computer modeling. The complex formation, binding properties, and conformational changes were investigated, providing insights into the transportation and distribution mechanisms of LEE in the human body.