Khan Mohammad Rashid, Khan Mohd Shahnawaz, Manoharan Rupavarshini, Karthikeyan Subramani, Alhosaini Khaled, Odeibat Humza Ahmad Mohammad, Ahmad M D Irshad, Al-Okail Majed, Al-Twaijry Nojood
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia.
Department of Biochemistry, College of Science, King Saud University, 11451, Riyadh, Saudi Arabia.
J Fluoresc. 2025 Jan;35(1):29-42. doi: 10.1007/s10895-023-03485-9. Epub 2023 Nov 16.
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.
肌肽是β-丙氨酰组氨酸，一种二肽，由肌肽合酶在我们体内内源性产生。它是一种抗氧化剂，因此能保护机体免受晚期糖基化终产物（AGEs）的有害影响。同样，氨基胍（AG）也通过清除自由基如活性氧（ROS）/活性羰基物种（RCS）来防止AGEs的形成。本研究使用实验和计算技术对肌肽和AG及其对糖化人血清白蛋白（HSA）的抑制特性进行了比较分析。果糖介导的白蛋白糖基化产生了荧光结构，如戊糖苷和丙二醛。这些AGEs被肌肽和AG显著降低。在20 mM时，肌肽和AG分别使戊糖苷荧光猝灭66%和83%。对丙二醛也观察到类似的抑制作用。在肌肽和AG存在的情况下，蛋白质的疏水性和色氨酸荧光得以恢复。氨基胍减少了HSA中的纤维化，而肌肽对聚集/纤维化没有显著影响。此外，分子对接研究观察到HSA-氨基胍和HSA-肌肽复合物的结合分数分别为-5.90 kcal/mol和-2.59 kcal/mol。氨基胍与ARG A:10形成一个传统氢键，并与胺基的ASP A:13、ASP A:259、ASP A:255和ASP A:256形成一个盐桥。同样，肌肽仅与胺基和羟基的GLU A:501和GLN A:508形成氢键。从模拟研究计算得出的HSA-氨基胍复合物的均方根偏差（RMSD）在70 ns内为1 nm，而HSA-肌肽的光谱有显著偏差且不稳定。氨基胍的优越抑制活性可能归因于与白蛋白的额外盐桥结合。总之，氨基胍可能是糖尿病相关神经疾病的更好治疗选择。
