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Inhibitory Potential of Carnosine and Aminoguanidine Towards Glycation and Fibrillation of Albumin: In-vitro and Simulation Studies

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Abstract

Carnosine is beta-alanyl histidine, a dipeptide, endogenously produced in our body by the carnosine synthase enzyme. It is an antioxidant, thus protecting from the deleterious effect of advanced glycation end products (AGEs). Similarly, aminoguanidine (AG) also prevents AGEs formation by scavenging free radicals such as reactive oxygen species (ROS)/reactive carbonyl species (RCS). This study used experimental and computational techniques to perform a comparative analysis of carnosine and AG and their inhibiting properties against glycated human serum albumin (HSA). Fructose-mediated glycation of albumin produced fluorescent structures, such as pentosidine and malondialdehyde. These AGEs were significantly reduced by carnosine and AG. At 20 mM, carnosine and AG quenches pentosidine fluorescence by 66% and 83%, respectively. A similar inhibitory effect was observed for malondialdehyde. Protein hydrophobicity and tryptophan fluorescence were restored in the presence of carnosine and AG. Aminoguanidine decreased fibrillation in HSA, while carnosine did not significantly affect aggregation/fibrillation. In addition, molecular docking study observed binding scores of -5.90 kcal/mol and -2.59 kcal/mol by HSA-aminoguanidine and HSA-carnosine complex, respectively. Aminoguanidine forms one conventional hydrogen bond with ARG A:10 and a salt bridge with ASP A:13, ASP A:259, ASP A:255, and ASP A:256 from the amine group. Similarly, carnosine forms only hydrogen bonds with GLU A:501 and GLN A:508 from the amine and hydroxy group. The root mean square deviation (RMSD) calculated from simulation studies was 1 nm upto 70 ns for the HSA-aminoguanidine complex and the spectrum of HSA-carnosine was significantly deviated and not stabilized. The superior inhibitory activity of aminoguanidine could be due to additional salt bridge bonding with albumin. Conclusively, aminoguanidine can be the better treatment choice for diabetes-associated neurological diseases.

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This manuscript's results/data/figures have not been published elsewhere, nor are they under consideration by another publisher. The data supporting this study's outcomes are available on request from the corresponding author.

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Funding

MSK acknowledges the generous support from the Research Supporting Project (RSP2023R352) by the King Saud University, Riyadh, Kingdom of Saudi Arabia.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia

    Mohammad Rashid Khan & Khaled Alhosaini

  2. Department of Biochemistry, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia

    Mohd Shahnawaz Khan, Humza Ahmad Mohammad Odeibat, Majed Al-Okail & Nojood Al-twaijry

  3. Division of Physics, School of Advanced Sciences, Vellore Institute of Technology University, Chennai Campus, Chennai, 600127, India

    Rupavarshini Manoharan

  4. Centre for Healthcare Advancement, Innovation and Research, Vellore Institute of Technology University, Chennai Campus, Chennai, 600127, India

    Subramani Karthikeyan

  5. Department of Structural Biology, School of Medicine, UTHEALTH Science Centre, San Antonio, TX, 78229, USA

    MD. Irshad Ahmad

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  1. Mohammad Rashid Khan
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Contributions

M.S.K, M.R.K, R.M, S.K designed and performed experiment. K.A, H.O, M.A analysis of data and result. M.A.O and N.A provided facility and support for chemicals and lab.

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Correspondence to Mohd Shahnawaz Khan.

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Khan, M.R., Khan, M.S., Manoharan, R. et al. Inhibitory Potential of Carnosine and Aminoguanidine Towards Glycation and Fibrillation of Albumin: In-vitro and Simulation Studies. J Fluoresc (2023). https://doi.org/10.1007/s10895-023-03485-9

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