Binding strength of the anti-diabetic drugs chlorpropamide (CPM) and tolbutamide (TBM) with model protein bovine serum albumin (BSA) shows strong modulation in presence of colloidal gold nanoparticles (AuNP). Intrinsic tryptophan fluorescence of both the native BSA and BSA-AuNP conjugate quenched in presence of the drugs. Stern-Volmer quenching constant (KSV) of CPM binding to BSA-AuNP conjugate at different temperatures is almost twice (6.76~14.76 × 103 M−1) than the corresponding values in native BSA (3.21~5.72 × 103 M−1). However, the calculated KSV values with TBM show certain degree of reduction in presence of AuNP (6.46× 103 M−1), while comparing with native BSA (8.83 × 103 M−1). The binding mode of CPM towards BSA-AuNP conjugate is mainly through hydrophobic forces; whereas, TBM binding is identified to be Van der Waal’s and hydrogen bonding type of interaction. Fluorescence lifetime analysis confirms static type of quenching for the intrinsic tryptophan fluorescence of BSA as well as BSA-AuNP conjugate with addition of CPM and TBM at different concentrations. The α-helical content in the secondary structure of BSA is decreased to 48.32% and 45. 28% in presence of AuNP, when the concentration of CPM is 0.08 mM and 0.16 mM in comparison with that of native protein (50.13%). On the other hand, the intensity of sugar induced advanced glycated end (AGE) product fluorescence is decreased by 55% and 80% at 0.13 nM and 0.68 nM AuNP, respectively. Change in the binding strength of the drugs with transport protein and reduced AGE product formation in presence of AuNP could lead to a major development in the field of nanomedicine and associated drug delivery techniques.
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Szkudlarek A, Pożycka J, Maciążek-Jurczyk M (2018) Influence of Piracetam on Gliclazide—Glycated Human Serum Albumin Interaction A Spectrofluorometric Study Molecules:24. https://doi.org/10.3390/molecules24010111
Kosecki SM, Rodgers PT, Adams MB (2005) Glycemic monitoring in diabetics with sickle cell plus β-thalassemia Hemoglobinopathy. Ann Pharmacother 39:1557–1560
Parim B, Uddandrao VVS, Saravanan G (2019) Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy. Heart Fail Rev 24:279–299
Vernon Roohk H, Zaidi AR (2008) A review of Glycated albumin as an intermediate Glycation index for controlling diabetes. J Diabetes Sci Technol 2:1114–1121
Sharma C, Kaur A, Thind SS, Singh B, Raina S (2015) Advanced glycation end-products (AGEs): an emerging concern for processed food industries. J Food Sci Technol 52:7561–7576
Hinton DJS, Ames JM (2006) Site specificity of glycation and carboxymethylation of bovine serum albumin by fructose. Amino Acids 30:425–434
Vetter SW, Glycated Serum Albumin and AGE Receptors, in: G.S. Makowski (Ed.) Advances in Clinical Chemistry, Ch 5, Elsevier, 2015, pp. 205–275
Uversky VN, Ashraf JM, Rabbani G, Ahmad S, Hasan Q, Khan RH, Alam K, Choi I (2015) Glycation of H1 histone by 3-Deoxyglucosone: effects on protein structure and generation of different advanced Glycation end products. Plos one, 10, https://doi.org/10.1371/journal.pone.0130630
Abbas G, Al-Harrasi AS, Hussain H, Hussain J, Rashid R, Choudhary MI (2016) Antiglycation therapy: discovery of promising antiglycation agents for the management of diabetic complications. Pharm Biol 54:198–206
Rahnama E, Mahmoodian-Moghaddam M, Khorsand-Ahmadi S, Saberi MR, Chamani J (2014) Binding site identification of metformin to human serum albumin and glycated human serum albumin by spectroscopic and molecular modeling techniques: a comparison study. J Biomol Struct Dyn 33:513–533
Arasteh A, Farahi S, Habibi-Rezaei M, Moosavi-Movahedi AA (2014) Glycated albumin: an overview of the in vitro models of an in vivo potential disease marker. Journal of Diabetes & Metabolic Disorders 13:49. https://doi.org/10.1186/2251-6581-13-49
Liu W, Cohenford MA, Frost L, Seneviratne C, Dain JA (2014) Inhibitory effect of gold nanoparticles on the D-ribose glycation of bovine serum albumin. Int J Nanomedicine 9:5461–5469
Seneviratne C, Narayanan R, Liu W, Dain JA (2012) The in vitro inhibition effect of 2 nm gold nanoparticles on non-enzymatic glycation of human serum albumin. Biochem Biophys Res Commun 422:447–454
Grueso E, Giráldez-Pérez RM, Perez-Tejeda P, Roldán E, Prado-Gotor R (2019) What controls the unusual melting profiles of small AuNPs/DNA complexes. Phys Chem Chem Phys 21:11019–11032
Chantada-Vázquez MP, López AC, Bravo SB, Vázquez-Estévez S, Acea-Nebril B, Núñez S (2019) Proteomic analysis of the bio-corona formed on the surface of (au, Ag, Pt)-nanoparticles in human serum. Colloids Surf B: Biointerfaces 177:141–148
Mosquera J, García I, Henriksen-Lacey M, González-Rubio G, Liz-Marzán LM (2019) Reducing protein Corona formation and enhancing colloidal stability of gold nanoparticles by capping with silica monolayers. Chem Mater 31:57–61
Lage ACP, Chaves CR, Frezard FJG, Aguilar JLL, Ladeira LO, de Almeida, RFM, Toshio R, Ferreira SR, Gold nanoparticles coated by antibiotics, and its production method, pharmaceutical compositions for treatment of infectious diseases, in: Braz. Pedido, 2018
Boussoufi F, Gallon SMN, Chang R, Webster TJ (2018) Synthesis and study of cell-penetrating peptide-modified gold nanoparticles. Int J Nanomedicine 13:6199–6205
Yeshchenko OA, Kutsevol NV, Naumenko AP (2016) Light-induced heating of gold nanoparticles in colloidal solution: dependence on detuning from surface Plasmon resonance. Plasmonics 11:345–350
Son S, Deepagan VG, Shin S, Ko H, Min J, Um W, Jeon J, Kwon S, Lee ES, Suh M, Lee DS, Park JH (2018) Ultrasmall gold nanosatellite-bearing transformable hybrid nanoparticles for deep tumor penetration. Acta Biomater 79:294–305
Levy R, Thanh NT, Doty RC, Hussain I, Nichols RJ, Schiffrin DJ, Brust M, Fernig DG (2004) Rational and combinatorial design of peptide capping ligands for gold nanoparticles. J Am Chem Soc 126:10076–10084
Wei M, Gao Y, Li X, Serpe MJ (2017) Stimuli-responsive polymers and their applications. Polym Chem 8:127–143
Yan M, Ge J, Liu Z, Ouyang P (2006) Encapsulation of single enzyme in Nanogel with enhanced biocatalytic activity and stability. J Am Chem Soc 128:11008–11009
Darby JF, Atobe M, Firth JD, Bond P, Davies GJ, O'Brien P, Hubbard RE (2017) Increase of enzyme activity through specific covalent modification with fragments. Chem Sci 8:7772–7779
Jonkheijm P, Weinrich D, Schröder H, Niemeyer CM, Waldmann H (2008) Chemical strategies for generating protein biochips. Angew Chem Int Ed 47:9618–9647
Wang L, Li X, Yuan L, Wang H, Chen H, Brash JL (2015) Improving the protein activity and stability under acidic conditions via site-specific conjugation of a pH-responsive polyelectrolyte. J Mater Chem B 3:498–504
Yohan D, Cruje C, Lu X, Chithrani DB (2016) Size-dependent gold nanoparticle interaction at Nano–micro Interface using both monolayer and multilayer (tissue-like) cell models. Nano-Micro Letters 8:44–53
Sotnikov DV, Berlina AN, Ivanov VS, Zherdev AV, Dzantiev BB (2019) Adsorption of proteins on gold nanoparticles: one or more layers? Colloids Surf B: Biointerfaces 173:557–563
Yang H, Wang M, Zhang Y, Li F, Yu S, Zhu L, Guo Y, Yang L, Yang S (2019) Conformational-transited protein corona regulated cell-membrane penetration and induced cytotoxicity of ultrasmall au nanoparticles. RSC Adv 9:4435–4444
Singh P, Pandit S, Mokkapati VRSS, Garg A, Ravikumar V, Mijakovic I (2018) Gold nanoparticles in diagnostics and therapeutics for human Cancer, international journal of molecular sciences 19 doi: https://doi.org/10.3390/ijms19071979
Shemetov AA, Nabiev I, Sukhanova A (2012) Molecular interaction of proteins and peptides with nanoparticles. ACS Nano 6:4585–4602
Brancolini G, Bellucci L, Maschio MC, Felice RD, Corni S (2019) The interaction of peptides and proteins with nanostructures surfaces: a challenge for nanoscience. Curr Opin Colloid Interface Sci 41:86–94
Schmeltz L, Metzger B (2007) Diabetes/Syndrome X. In: Taylor JB, Triggle DJ (eds) Comprehensive medicinal chemistry II. Elsevier, Oxford, pp 417–458
Thulé PM, Umpierrez G (2014) Sulfonylureas: a new look at old therapy. Current Diabetes Reports 14:473
Seino S, Takahashi H, Takahashi T, Shibasaki T (2012) Treating diabetes today: a matter of selectivity of sulphonylureas. Diabetes Obes Metab 14:9–13
Wei Y, Han CS, Zhou J, Liu Y, Chen L, He RQ (2012) D-ribose in glycation and protein aggregation. Biochim Biophys Acta Gen Subj 1820:488–494
Wells-Knecht KJ, Zyzak DV, Litchfield JE, Thorpe SR, Baynes JW (1995) Identification of Glyoxal and arabinose as intermediates in the Autoxidative modification of proteins by glucose. Biochemistry 34:3702–3709
Enustun BV, Turkevich J (1963) Coagulation of colloidal gold. J Am Chem Soc 85:3317–3328
Haiss W, Thanh NTK, Aveyard J, Fernig DG (2007) Determination of size and concentration of gold Nanoparticles from UV−Vis spectra. Anal Chem 79:4215–4221
Singh IR, Mitra S (2019) Interaction of chlorpropamide with serum albumin: effect on advanced glycated end (AGE) product fluorescence. Spectrochim Acta A Mol Biomol Spectrosc 206:569–577
Wahba MEK, El-Enany N, Belal F (2015) Application of the stern–Volmer equation for studying the spectrofluorimetric quenching reaction of eosin with clindamycin hydrochloride in its pure form and pharmaceutical preparations. Anal Methods 7:10445–10451
Lehrer S (1971) Solute perturbation of protein fluorescence. Quenching of the tryptophyl fluorescence of model compounds and of lysozyme by iodide ion Biochemistry 10:3254–3263
Valeur B (2002) Molecular fluorescence principles and applications. Wiley-VCH, Weinheim, FRG
Lakowicz JR, Principles of fluorescence spectroscopy, in, Springer Singapore, 2006
Chakraborty S, Joshi P, Shanker V, Ansari ZA, Singh SP, Chakrabarti P (2011) Contrasting effect of gold nanoparticles and Nanorods with different surface modifications on the structure and activity of bovine serum albumin. Langmuir 27:7722–7731
Klotz IM, Hunston DL (1971) Properties of graphical representations of multiple classes of binding sites. Biochemistry 10:3065–3069
Maciążek-Jurczyk M (2014) Phenylbutazone and ketoprofen binding to serum albumin. Fluorescence study. Pharmacol Rep 66:727–731
Esmaeilzadeh S, Valizadeh H, Zakeri-Milani P (2017) The effects of pH, temperature and protein concentration on the in vitro binding of flutamide to human serum albumin. Pharm Dev Technol 22:982–991
Ross PD, Subramanian S (1981) Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20:3096–3102
Østdal H, Andersen HJ (1996) Non-enzymic protein induced hydrolysis of P-nitrophenyl acyl esters in relation to lipase/esterase assays. Food Chem 55:55–61
Watanabe H, Tanase S, Nakajou K, Maruyama T, Kragh-Hansen U, Otagiri M (2000) Role of arg-410 and tyr-411 in human serum albumin for ligand binding and esterase-like activity. Biochem J 349:813–819
Patel R, Maurya N, Parray M, Farooq N, Siddique A, Verma KL, Dohare N (2018) Esterase activity and conformational changes of bovine serum albumin toward interaction with mephedrone: spectroscopic and computational studies. J Mol Recognit 31:e2734
Salahuddin P, Rabbani G, Khan RH (2014) The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach. Cell Mol Biol Lett 19:407–437
Kessel L, Kalinin S, Nagaraj RH, Larsen M, Johansson LBA (2002) Time-resolved and steady-state fluorescence spectroscopic studies of the human Lens with comparison to Argpyrimidine, Pentosidine and 3-OH-kynurenine. Photochem Photobiol 76:549–554
Sell DR, Monnier VM (1989) Isolation, purification and partial characterization of novel fluorophores from aging human insoluble collagen-rich tissue. Connect Tissue Res 19:77–92
Cervantes-Laurean D, Schramm DD, Jacobson EL, Halaweish I, Bruckner GG, Boissonneault GA (2006) Inhibition of advanced glycation end product formation on collagen by rutin and its metabolites. J Nutr Biochem 17:531–540
Obayashi H, Nakano K, Shigeta H, Yamaguchi M, Yoshimori K, Fukui M, Fujii M, Kitagawa Y, Nakamura N, Nakamura K, Nakazawa Y, Ienaga K, Ohta M, Nishimura M, Fukui I, Kondo M (1996) Formation of Crossline as a fluorescent advanced Glycation end product in vitro and in vivo. Biochem Biophys Res Commun 226:37–41
Hori M, Yagi M, Nomoto K, Ichijo R, Shimode A, Kitano T, Yonei Y (2012) Experimental models for advanced Glycation end product formation using albumin, collagen, elastin, keratin and proteoglycan. Anti-Ageing Medicine 9:125–134
Hayase F (2000) Recent development of 3-Deoxyosone related Maillard reaction products. Food Sci Technol Res 6:79–86
Kim H, Patel MS (1992) Characterization of two site-specifically mutated human dihydrolipoamide dehydrogenases (His-452----Gln and Glu-457----Gln). J Biol Chem 267:5128–5132
Gkogkolou P, Bohm M (2012) Advanced glycation end products: key players in skin aging? Dermato-endocrinology 4:259–270
Singh VP, Bali A, Singh N, Jaggi AS (2014) Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol 18:1–14
Das NK, Pawar L, Kumar N, Mukherjee S (2015) Quenching interaction of BSA with DTAB is dynamic in nature: a spectroscopic insight. Chem Phys Lett 635:0–55
Szkudlarek A, Pentak D, Ploch A, Pożycka J, Maciążek-Jurczyk M (2017) Effect of Temperature on Tolbutamide Binding to Glycated Serum Albumin, Molecules:22. https://doi.org/10.3390/molecules22040569
Dolatabadi JEN, Panahi-Azar V, Barzegar A, Jamali AA, Kheirdoosh F, Kashanian S, Omidi Y (2014) Spectroscopic and molecular modeling studies of human serum albumin interaction with propyl gallate. RSC Adv 4:64559–64564
Du X, Li Y, Xia Y-L, Ai S-M, Liang J, Sang P, Ji X-L, Liu S-Q (2016) Insights into protein–ligand interactions: mechanisms, models, and methods. Int J Mol Sci 17(2):144. https://doi.org/10.3390/ijms17020144
Zhang L, Lu Y, Ye YH, Yang SH, Tu ZC, Chen J, Wang H, Wang HH, Yuan T (2019) Insights into the mechanism of Quercetin against BSA-fructose Glycation by spectroscopy and high-resolution mass spectrometry: effect on physicochemical properties. J Agric Food Chem 67:236–246
Tsai DH, DelRio FW, Keene AM, Tyner KM, MacCuspie RI, Cho TJ, Zachariah MR, Hackley VA (2011) Adsorption and conformation of serum albumin protein on gold nanoparticles investigated using dimensional measurements and in situ spectroscopic methods. Langmuir 27:2464–2477
Millan S, Kumar A, Satish L, Susrisweta B, Dash P, Sahoo H (2018) Insights into the binding interaction between copper ferrite nanoparticles and bovine serum albumin: an effect on protein conformation and activity. Luminescence 33:990–998
Ning C, Segal S (2000) Plasma galactose and galactitol concentration in patients with galactose-1-phosphate uridyltransferase deficiency galactosemia: determination by gas chromatography/mass spectrometry. Metabolism 49:1460–1466
Kawasaki T, Akanuma H, Yamanouchi T (2002) Increased fructose concentrations in blood and urine in patients with diabetes. Diabetes Care 25:353–357
The authours acknowledge the support from Department of Nanotechnology, NEHU for the characterization of BSA-AuNP conjugate. Thanks are also due to the Dept. of Science & Technology (DST), Govt. of India for supporting the Chemistry Department through FIST program (SR/FST/CSI-194/2008). IRS is a recipient of research fellowship from NEHU.
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• The formation of the BSA-AuNP conjugate is confirmed by the IR spectroscopy.
• Binding efficiency of CPM and TBM to native BSA are strongly modulated in presence AuNP.
• CPM binds to BSA-AuNP conjugate mainly through hydrophobic forces.
• Binding of TBM to BSA-AuNP conjugate through van der Waals and HB interactions.
• AuNP induces strong inhibition towards the glycation of serum proteins.
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Singh, I.R., Mitra, S. Modulated Protein Binding Ability of Anti-Diabetic Drugs in Presence of Monodispersed Gold Nanoparticles and its Inhibitory Potential towards Advanced Glycated End (AGE) Product Formation. J Fluoresc (2020). https://doi.org/10.1007/s10895-019-02485-y
- Serum albumin
- Drug binding
- AGE product