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Immune Systems, Molecular Diagnostics, and Bionanotechnology
Published in Anil Kumar Anal, Bionanotechnology, 2018
Energy is required for the formation antigen–antibody complex, which also regulates the molecular specificity of antibodies. The binding strength of paratope of an antibody with the epitope of specific antigen is known as antibody affinity, which in turn is the sum total of attractive force and repulsive force. The binding strength required for binding between all sites of multivalent antigen and antibody is known as avidity, and hence is higher than affinity (Božič et al. 2014). In case of high affinity, epitope fits exactly in the paratope (lock and key interaction), whereas in case of low affinity, epitopes are loosely held in the paratope (Day 2015). Small portion of molecules involving few amino acids and small surface area between 0.4 and 8 nm2 are involved in antigen–antibody interactions, which also have to overcome repulsive force. When antigens and antibodies are at several nanometer distances, they come together by attractive forces such as ionic bond, hydrophobic bond, and overcome the hydration energies by removing water molecules and come even more closer because of van der Waals force along with ionic strength. The binding strength of antigen–antibody complex at this condition depends on the contact area and goodness of fit between surfaces (Reverberi and Reverberi 2007).
History of Aptamer Development
Published in Rakesh N. Veedu, Aptamers, 2017
Nasa Savory, Koichi Abe, Taiki Saito, Kazunori Ikebukuro
The strength of interactions in which multiple binding sites simultaneously interact with the target is known as avidity, particularly for antibody–antigen interactions. In aptamers, multimerization of single or multiple aptamers often offers dramatically higher affinity and specificity than monovalent binding. We have shown that the dimerization of two thrombin-binding aptamers (TBAs) that interact with different target sites of thrombin increased affinity for thrombin [50]. The dimerized thrombin aptamer was designed by tandem attachment of a 15-nt TBA (TBA15) [51] and a 29-nt TBA (TBA29) [52] through 0-, 5-, 10-, or 20-nt thymine linkers. The dimerization led to decreased dissociation constant (koff) values; thus, it led to improvement of the dissociation constant (KD) for thrombin binding. In addition, the dimerization study of TBAs indicated that the lengths of linker oligonucleotides are important for the dimerized aptamer’s inhibitory activity toward fibrinogen degradation by thrombin. A dimerized VEGF-binding aptamer was also developed, resulting in improvement of affinity for VEGF [50].
Nanocarriers as an Emerging Platform for Cancer Therapy
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Dan Peer, Jeffrey M. Karp, Seungpyo Hong, Omid C. Farokhzad, Rimona Margalit, Robert Langer
Antibodies may be used in their native state or as fragments for targeting (Fig. 2.2a). However, use of whole mAbs is advantageous because the presence of two binding sites (within a single antibody) gives rise to a higher binding avidity. Furthermore, when immune cells bind to the Fc portion of the antibody, a signalling cascade is initiated to kill the cancer cells. However, the Fc domain of an intact mAb can also bind to the Fc receptors on normal cells, as occurs with macrophages. This may lead to increased immunogenicity—the ability to evoke an immune response—and liver and spleen uptake of the nanocarrier. An additional advantage of whole/intact antibodies is their ability to maintain stability during long-term storage. Although antibody fragments including antigen-binding fragments (Fab), dimers of antigen-binding fragments (F(ab’)2), single-chain fragment variables (scFv) and other engineered fragments are less stable than whole antibodies, they are considered safer when injected systemically owing to reduced non-specific binding [16, 30]. To rapidly select antibodies or their fragments that bind to and internalize within cancer cells, phage display libraries that involve a high throughput approach may be used [31, 32]. This method generates a multitude of potentially useful antibodies that bind to the same target cells but to different epitopes (a part of a macromolecule that is recognized by antibodies; one receptor may have several epitopes that will be recognized by multiple antibodies). For example, through a selective process, scFv antibodies have been identified for superior binding and internalization properties for prostate cancer cells [33].
Nuclear Medicine in Oncology
Published in Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization, 2018
Carla Oliveira, Rui Parafita, Ana Canudo, Joana Correia Castanheira, Durval C. Costa
Other subsequently developed radiopharmaceuticals are 18F-fluorocholine and, more recently, 68Ga-labelled prostate-specific membrane antigen (PSMA) ligand, both potentially recommended for the staging and restaging of prostatic carcinoma, usually with no significant 18F-FDG avidity. 18F-fluorocholine is a choline analogue, which is an integral part of the cell membrane, and is mostly taken up by cells with a greater proliferative index and, therefore, with an increased metabolism of the cell membrane, such as the neoplastic cells. 68Ga-labelled PSMA ligand binds to the cell surface protein that is overexpressed in prostate carcinoma and its metastases.