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Towards the Importance of Fenugreek Proteins
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Various inter-molecular interactions in proteins result in their low molecular mobility, as well as high softening or melting temperature. In other words, once the protein is folded to its final native form, it is stabilized through hydrophobic and electrostatic interactions, hydrogen bonds, along with further strong covalent crosslinks. Softening of proteins requires their denaturation, meaning partial unfolding of structured native protein into an unstructured state with no or little fixed residual structures. Consequently, melting temperature of proteins could be considered as their denaturation temperature (Td). However, a complete unfolding into a fully amorphous structure may not occur as true melting means (Ricci et al., 2018). Considering that any changes in secondary, tertiary, or quaternary structures of proteins may refer to proteins denaturation, DSC not only gives insights into the differences between thermal characteristics of various proteins like legumes, but also could help to study the effects of various parameters on those attributes. Generally, denaturation of proteins is an endothermic process, owing to the heat they absorb to thermally unfold over a temperature range.
Melt Granulation
Published in Dilip M. Parikh, Handbook of Pharmaceutical Granulation Technology, 2021
Shana Van de Steene, Valérie Vanhoorne, Chris Vervaet, Thomas De Beer
The critical process parameters are the homogeneity of the solubilized or dispersed mixture, the processing temperature, the viscosity of the formulation, and the cooling capacity to ensure rapid and uniform solidification of the droplets during prilling. If the mixture is not homogeneous, the drug concentration varies per droplet and viscosity fluctuations influence the droplet formation rate and uniformity. Generally, the processing temperature is 10°C above the melting temperature of the lipids present in the formulation, and a viscosity limit of 500 mPas is applied [39,51].
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Whereas DNA and RNA have deoxyribose and ribose sugar backbones, respectively, the PNA backbone is comprised of repeating N-(2-aminoethyl)-glycine units linked by peptide bonds (Figure 5.95). The various purine and pyrimidine bases are linked to the backbone by a methylene bridge and a carbonyl group. PNAs are analogous to peptides, with the N-terminus at the first (left) position and the C-terminus at the last (right) position. Since the backbone of PNA contains no charged phosphate groups, the binding between PNA/DNA strands is stronger than between DNA/DNA strands due to the lack of electrostatic repulsion. Early experiments with homopyrimidine strands showed that the melting temperature (Tm) of a 6-base thymine PNA/adenine DNA double helix was 31°C in comparison to an equivalent 6-base DNA/DNA duplex that denatured at less than 10°C. Interestingly, the affinity between two PNA/PNA oligomers is greater than that between equivalent lengths of PNA/DNA oligomers.
Drug-like antibodies with high affinity, diversity and developability directly from next-generation antibody libraries
Published in mAbs, 2021
Andre Azevedo Reis Teixeira, Michael Frank Erasmus, Sara D’Angelo, Leslie Naranjo, Fortunato Ferrara, Camila Leal-Lopes, Oliver Durrant, Cecile Galmiche, Aleardo Morelli, Anthony Scott-Tucker, Andrew Raymon Morton Bradbury
The developability assays used here were selected based on their widespread acceptance and non-redundant ability to assess relevant properties in a large study of the biophysical characteristics of clinical-stage antibodies.3 Some act as surrogates for properties desired in an antibody but not directly quantifiable as a meaningful characteristic. Melting temperature (Tm), for example, is often considered an important parameter when generating new libraries for therapeutic purposes.32,33,61 However, the analysis shows no correlation between the Tm of therapeutic antibodies and other relevant properties such as aggregation and specificity, and only a weak correlation with antibody expression titer (Spearman coefficient = 0.35). For example, rilotumumab (anti-hepatocyte growth factor, Amgen Inc), while being highly thermostable (Tm 79°C), performed poorly in an accelerated stability study in solution (the worst of all the tested antibodies), and among the scaffolds we chose, evolocumab has the lowest reported Tm (65°C), while having the highest reported expression titer (260.7 mg/ml).3
Impact of IgG subclass on molecular properties of monoclonal antibodies
Published in mAbs, 2021
Yu Tang, Paul Cain, Victor Anguiano, James J. Shih, Qing Chai, Yiqing Feng
We observed a significant impact of the variable region and IgG subclass on thermal stability (Figure 1). Consistent with previous reports,12,13,21,22 the first melting temperatures, presumably reflecting the CH2 domain unfolding, largely remain the same within each IgG subclass. The mutations in IgG1EN located in the CH2 domain led to a significantly lower CH2 melting temperature, analogous to some other IgG molecules with FcγR interactions modulated by either mutagenesis or deglycosylation.23–25 In this study, the individual domain melting temperature is difficult to determine unequivocally due to the overlapping transitions. Assuming that the highest peak in each thermogram represents Fab transition, the Fab melting temperature is affected by both variable domain and IgG subclass. Within each mAb series, the Tm of the Fab in IgG1 is virtually identical to that in IgG1EN, similar or slightly higher than that in IgG2 mAb, and higher than that in IgG4PAA. The observation of a decrease in Fab Tm changing from IgG1 to IgG4 is in agreement with a previous report by Heads et al.26 The mAbs with Fv A show higher Fab transition temperatures than the mAbs with either Fv B or Fv C. It has been reported that the unfolding temperature of antibodies could be correlated with the physical and chemical stability of the molecules at storage, accelerated degradation, and under other stress conditions.14,27,28 We are investigating the effect of the unfolding temperatures, especially the low CH2 unfolding temperature in IgG1EN, in another study.
Systematic implementation of quality-by-design (QbD) to develop NSAID-loaded nanostructured lipid carriers for ocular application: preformulation screening studies and statistical hybrid-design for optimization of variables
Published in Drug Development and Industrial Pharmacy, 2020
Vishal R. Rathod, Dhaval A. Shah, Rutesh H. Dave
In the NLC production, the first step was to heat the lipid phase (Dynasan®114-solid lipid and Miglyol®840-liquid lipid) and the aqueous phase (DI water and the surfactant mixture of Kolliphor®P188 and Kolliphor® HS15) separately and at the same temperature (65 °C). The lipid phase was heated to 65 °C, which is above the melting temperature of the solid lipid. Ibuprofen was added after the lipid matrix was melted. In the second step, the aqueous phase was carefully added to the lipid phase and subjected to high shear homogenizer (1000 rpm, 2 min) (Biospec Products, Bartlesville, OK, USA) to produce a primary emulsion. This sample was further subjected to ultrasonication (30 kHz, 3 min) using a probe sonicator (Misonix-S3000-Ultrasonic) and slowly cooled down to 4 °C and then stored in a refrigerator [17].