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Radionuclide-based Diagnosis and Therapy of Prostate Cancer
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Sven-Erik Strand, Mohamed Altai, Joanna Strand, David Ulmert
Direct radiohalogenation of targeting agents with radioiodine isotopes is usually a robust, fast labelling strategy with very high radiolabelling yields [31]. However, bromine and astatine are more resistant to oxidation, and attempts to directly radiobrominate and radioastatinate targeting agents have produced fairly low labelling yields and inconsistent results [34]. Moreover, the tyrosine residues, used for isotope binding in direct halogenation, may in some targeting agents be located in crucial target recognizing/binding sites on the targeting vector, thus comprising its immunoreactivity. Similarly, some disulphide bonds crucial for maintaining the targeting protein tertiary structure may be vulnerable to harsh reduction-oxidation conditions of direct radiohalogenation.
Structure and function of skin
Published in Roger L. McMullen, Antioxidants and the Skin, 2018
The reticular layer of the dermis is bordered above by the papillary layer and below by the hypodermis. Collagen I, which is arranged in large bundles, constitutes the largest population of collagen in this layer. The density of the fibers is much greater in this layer than in the papillary dermis. Collagen is arranged into fibrils or bundles and the elastic fibers are intertwined within this network. Typically, four different types of collagen are present in the dermis and consist of types I, III, V, and VI, but mostly types I and III. Collagen has a polypeptide sequence that follows the scheme, Gly-X-Y, where X and Y correspond to proline and 4-hydroxyproline, respectively. In terms of secondary structure, collagen contains three alpha chains (not to be confused with alpha helices) that are supertwisted (protein tertiary structure) together to provide its fibril structure.15
Aspartic Acid Racemization on Aging
Published in Sara C. Zapico, Mechanisms Linking Aging, Diseases and Biological Age Estimation, 2017
Sara C. Zapico, Christian Thomas, Sofía Tirados Menéndez
In humans, age-related diseases of the bone and the cartilage occur with altered levels of racemization of Aspartic acid. Racemization can impact protein conformation through reorientation of the angles of peptide bonds, thus affecting electrostatic interactions responsible for protein tertiary structure (Hol et al. 1981). Furthermore, racemization destabilizes the Collagen triple helix (Shah et al. 1999) and modifications in the structure of Collagen type I have been involved in the reduced bone strength seen in Osteoporosis (Boskey et al. 1999). Following this reasoning, studies performed in postmenopausal women demonstrated an association between higher levels of age-related forms of Asp in Collagen type I and an increased risk of osteoporotic fracture (Garnero et al. 2002). In addition, the levels of D-Asp in Collagen from cartilage diagnosed with osteoarthrosis are reduced due to the synthesis of new proteins in an attempt to repair the damage caused by the disease (Stabler et al. 2009). Interestingly, a recent study questioned whether protein turnover in osteoarthritic cartilage depends on joint site. The authors reported a higher anabolic metabolism in the knee when compared with the hip (Catterall et al. 2015), although the results cannot clarify if this difference indicates distinct mechanisms of disease progression or if it is a result of different cartilage biology.
Current advances in biopharmaceutical informatics: guidelines, impact and challenges in the computational developability assessment of antibody therapeutics
Published in mAbs, 2022
Rahul Khetan, Robin Curtis, Charlotte M. Deane, Johannes Thorling Hadsund, Uddipan Kar, Konrad Krawczyk, Daisuke Kuroda, Sarah A. Robinson, Pietro Sormanni, Kouhei Tsumoto, Jim Warwicker, Andrew C.R. Martin
Biopharmaceutical informatics tools are widely used for in silico screening of biophysical properties in an antibody library. These antibody informatics approaches have been used to evaluate key biochemical and biophysical properties such as solubility, stability, viscosity, charge profiles, posttranslational modifications (PTMs), pharmacokinetic and pharmacodynamic (PK/PD) profiles, and hydrophobicity to rank the candidates. The prediction of protein tertiary structure is accomplished by either homology modeling approaches, fold recognition, or ab initio modeling approaches when similar sequences with known structures are absent. Several studies have implemented homology modeling to calculate the biochemical and biophysical properties of a mAb library.16–18 Specific homology modeling algorithms for antibodies have been developed for better accuracy and representation.19–21 In general, antibody sequences and structures are well conserved except for the complementarity-determining regions (CDRs). The CDRs, except for CDR-H3, can be classified into a set of limited conformations called canonical structures22–24 that can be predicted from sequence key residues, enabling sub-ångström accuracy in structure prediction. However, predicting conformations of CDR-H3 is still challenging because it is the most diverse both in sequence and structure.25 Sequence-structure correlations identified for CDR-H3 have been used as geometric constraints in simulations for structure prediction.26,27
Tracing protein and proteome history with chronologies and networks: folding recapitulates evolution
Published in Expert Review of Proteomics, 2021
Gustavo Caetano-Anollés, M. Fayez Aziz, Fizza Mughal, Derek Caetano-Anollés
At higher levels of organization, striking regularities exist in how secondary structures assemble into tightly packed layered arrangements of the polypeptide chain [54]. These regularities in connectivities and relative orientation of secondary structures (topologies and architectures, respectively), which result in part from physical and chemical properties that are intrinsic [55,56], are responsible for protein tertiary structure. Tertiary structure first manifests in the formation of autonomous folding elements known as protein structural domains (Figure 1A). Domains are structural [57], evolutionary [58] and functional [59] units of proteins, mainly because of their ‘compact globular’ folded structure [first observed by Phillips [60] in lysozyme], their high evolutionary conservation [61] and their recurrent association with molecular functions [62]. Since proteins often contain more than one domain, domains appear repeatedly, individually or combined with other domains sometimes in unusually complex arrangements [5]. This enhances domain recurrence. Tertiary structure also manifests in supradomains, domain combinations that behave as modules and appear recurrently in multidomain proteins [63].
Washingtonia filifera seed extracts inhibit the islet amyloid polypeptide fibrils formations and α-amylase and α-glucosidase activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Sonia Floris, Antonella Fais, Rosaria Medda, Francesca Pintus, Alessandra Piras, Amit Kumar, Piotr Marek Kuś, Gunilla Torstensdotter Westermark, Benedetta Era
The three-dimensional (3 D) structure of IAPP29 (PDB id: 2L86) and α-amylase30 (PDB id: 1DHK) were obtained from protein data bank. However, due to the unavailability of the experimental 3 D structure of an α-glucosidase protein from Saccharomyces cerevisiae, we performed a template-based homology modelling using Swiss-model web server31 with 3 D reference structure of isomaltase from Saccharomyces cerevisiae32 (PDB id: 3AJ7) having 72% sequence identity33 with the target protein structure. The predicted protein tertiary structure model was evaluated by local quality estimates34 and Ramachandran plot of the dihedrals. The 3 D structures of the ligands were obtained using open-babel software35; the details of ligand preparation have been described in our previous studies36,37. The docking experiment to generate and predict best protein-ligand complex pose was performed using a COACH-D server38.