Spectroscopic studies on the gemini surfactant mediated refolding of human serum albumin

Gull, Nuzhat; Khan, Javed Masood; Rukhsana, .; Khan, Rizwan

doi:10.1016/j.ijbiomac.2017.03.134

Cited by 21 publications

(10 citation statements)

References 45 publications

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“…Despite being systematically lower, the MW-calculated R h values of the investigated proteins correlated well with the DLS measurements (R 2 = 0.96, Figure 2A). Experimental values reported in the literature for two additional globular proteins, namely, human serum albumin (66 kDa; R h = 3.5 nm) 29 and α-2-macroglobulin (725 kDa; R h = 9.8 nm), 30 were included for comparison and showed good agreement with the results of this study (Figure 2B). Instead, a discrepancy was noted for two representative nonglobular proteins, α-synuclein (14.5 kDa; R h = 3.6 nm) 31 and fibrinogen (340 kDa; R h = 10.0 nm).…”

Section: Methodssupporting

confidence: 80%

Ocular Pharmacokinetics of Intravitreally Injected Protein Therapeutics: Comparison among Standard-of-Care Formats

et al. 2021

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The current standard of care for antivascular endothelial growth factor (VEGF) treatment requires frequent intravitreal (IVT) injections of protein therapeutics, as a result of limited retention within the eye. A thorough understanding of the determinants of ocular pharmacokinetics (PK) and its translation across species is an essential prerequisite for developing more durable treatments. In this work, we studied the ocular PK in macaques of the protein formats that comprise today’s anti-VEGF standard of care. Cynomolgus monkeys received a single IVT injection of a single-chain variable fragment (scFv, brolucizumab), antigen-binding fragment (Fab, ranibizumab), fragment crystallizable-fusion protein (Fc-fusion, aflibercept), or immunoglobulin G monoclonal antibody (IgG, VA2 CrossMAb). Drug concentrations were determined in aqueous humor samples collected up to 42 days postinjection using immunoassay methods. The ocular half-life (t 1/2) was 2.28, 2.62, 3.13, and 3.26 days for scFv, Fab, Fc-fusion, and IgG, respectively. A correlation with human t 1/2 values from the literature confirmed the translational significance of the cynomolgus monkey as an animal model for ocular research. The relation between ocular t 1/2 and molecular size was also investigated. Size was inferred from the molecular weight (MW) or determined experimentally by dynamic light scattering. The MW and hydrodynamic radius were found to be good predictors for the ocular t 1/2 of globular proteins. The analysis showed that molecular size is a determinant of ocular disposition and may be used in lieu of dedicated PK studies in animals.

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Section: Methodssupporting

confidence: 80%

Ocular Pharmacokinetics of Intravitreally Injected Protein Therapeutics: Comparison among Standard-of-Care Formats

et al. 2021

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“…The greater magnitude of the quenching rate constant value reveals that quenching occurs through a static mechanism rather than the dynamic procedure and consists of the ground state complex formation among 2(C 12 Cys) GS and HSA. 50−52…”

Section: Resultsmentioning

confidence: 99%

Molecular Interaction of Amino Acid-Based Gemini Surfactant with Human Serum Albumin: Tensiometric, Spectroscopic, and Molecular Docking Study

et al. 2019

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Binding effect and interaction of N,N′-dialkyl cystine based gemini surfactant (GS); 2(C12Cys) with human serum albumin (HSA) were systematically investigated by the techniques such as surface tension measurement, UV−visible spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and molecular docking studies. The surface tension measurement exhibited that HSA shifted the critical micelle concentration of the 2(C12Cys) GS to the higher side that confirms the complex formation among 2(C12Cys) GS and HSA which was also verified by UV–visible, fluorescence, and CD spectroscopy. Increase in the concentration of 2(C12Cys) GS increases the absorption of the HSA protein but has a reverse effect on the fluorescence intensity. The analysis of UV–visible study with the help of a static quenching method showed that the value acquired for the bimolecular quenching constant (kq) quenches the intrinsic fluorescence of the HSA protein. Synchronous fluorescence spectrometry declared that the induced-binding conformational changes in HSA and CD results explained the variations in the secondary arrangement of the protein in presence of 2(C12Cys) GS. The present study revealed that the interaction between 2(C12Cys) GS and HSA is important for the preparation and properties of medicines. Molecular docking study provides insight into the specific binding site of 2(C12Cys) GS into the sites of HSA.

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“…The detailed structural analysis of the above protein−surfactant complexes is reported using SANS data and supported by DLS measurements. 9,11,13,27,28 2. RESULTS AND DISCUSSION 2.1.…”

Section: Introductionmentioning

confidence: 99%

Unfolding and Refolding of Protein by a Combination of Ionic and Nonionic Surfactants

et al. 2018

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The interaction of protein and surfactant yields protein–surfactant complexes which have a wide range of applications in the cosmetics, foods, and pharmaceutical industries among others. Ionic and nonionic surfactants are known to interact differently with the protein. The interplay of electrostatic and hydrophobic interactions governs the resultant structure of protein–surfactant complexes. The present study enlightens the paramount role of the hydrophobic interaction, tuned by the hydrophobic tail length of ionic surfactants, in the unfolding of anionic bovine serum albumin (BSA) protein. The unfolding of BSA in the presence of four different tail-length cationic surfactants, that is, C10TAB, C12TAB, C14TAB, and C16TAB, has been investigated by small-angle neutron scattering and dynamic light scattering. All cationic surfactants unfold the protein at a certain concentration range. The propensity of protein unfolding increases with increasing the hydrophobic tail length. The denatured structure of BSA upon addition of cationic surfactants is characterized by the random flight model representing a beads-on-a-string chain-like complex. The unfolded protein binds the surfactant micelles in the protein–surfactant cluster. The micelles get elongated with the increasing concentration of cationic surfactants, whereas the number of micelles per cluster is decreased. In the final stage, the protein–surfactant cluster merges to one large micelle with unfolded protein wrapping the micelle surface. The pathway of protein unfolding is described in terms of the changes in the micellar size, the number of micelles formed per cluster, the separation between the micelles in the cluster, the aggregation number of micelles, and the number of proteins per cluster. The protein–surfactant interaction is further examined in the presence of a nonionic surfactant, that is, C12E10. The nonionic surfactant significantly suppresses the interaction of BSA protein with ionic surfactants by forming mixed micelles. As a result of the mixed micelles formation by ionic–nonionic surfactants, the ionic surfactant moves out from the unfolded BSA protein, and this enables the protein to refold back to its native structure. The propensity of mixed micelle-driven refolding of proteins is significantly changed with changing the tail length of the ionic surfactant.

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Spectroscopic studies on the gemini surfactant mediated refolding of human serum albumin

Cited by 21 publications

References 45 publications

Ocular Pharmacokinetics of Intravitreally Injected Protein Therapeutics: Comparison among Standard-of-Care Formats

Ocular Pharmacokinetics of Intravitreally Injected Protein Therapeutics: Comparison among Standard-of-Care Formats

Molecular Interaction of Amino Acid-Based Gemini Surfactant with Human Serum Albumin: Tensiometric, Spectroscopic, and Molecular Docking Study

Unfolding and Refolding of Protein by a Combination of Ionic and Nonionic Surfactants

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