Methods of Protein Iodination
Erwin Regoeczi in Iodine-Labeled Plasma Proteins, 2019
An acyl group is the univalent group, , where R is any organic group attached to one bond of the bivalent carbonyl group ,. The alkyl group has already been defined in Section C.1.a. An aryl group is an organic group derived from an aromatic hydrocarbon by the removal of a hydrogen (e.g., the phenyl group, C6H5-, derived from benzene, C6H6). Amines are organic derivatives of ammonia (NH3) formed by the replacement of one, two, or three of the hydrogen atoms by an alkyl or aryl group; correspondingly, the resulting aliphatic and aromatic (and other) amines are classified as primary (RNH2), secondary (R2NH), or tertiary (R3N) amines. Amides are carboxylic acid derivatives obtained by the replacement of the OH group of an acid by an amino group (NH2). Azo compounds are organic compounds which contain the group, -N:N-, attached to two alkyl or aryl groups (e.g., azobenzene, C6H5-N:N-C6H5). In contrast, only one of the two N atoms bonded together in diazo compounds is attached to a carbon of an organic structure (RN=N, see further below). Imines, containing the grouping, -CH=N-, arise from the condensation of primary amines with aldehydes (or ketones) through the loss of H2O. Imides are nitrogen analogs of anhydrides:
Medication: Nanoparticles for Imaging and Drug Delivery
Harry F. Tibbals in Medical Nanotechnology and Nanomedicine, 2017
Another type of photoactivation uses light-activated motion in molecules to open gates or induce motion in nanoparticles. The California NanoSystems Institute at the University of California at Los Angeles, Los Angeles, California has been especially productive in exploring the possibilities of this approach, and have dubbed their creations “nanoimpellers.” Photoactivated moving parts based on the photoisomerization of large planar molecules such as azo-benzene derivatives are used with mesoporous silica nanoparticles to regulate drug delivery from pores in the silica. The azobenzene derivatives, with substituents ranging from hydrogen atoms to dendrimers, transition from trans to cis isomers when interacting with the electromagnetic oscillation of a light beam. The change in conformation and size between the trans and cis isomers can be used to regulate the transport of molecules through pores to electrodes. A light-induced back-and-forth wagging motion has been demonstrated to act as a molecular impeller that regulates the release of molecules from the pores of silica nanoparticles under “remote control” upon photoexcitation [432-434]. This type of particle has been used experimentally to take up drugs and deliver them into cancer cells [435].
Neurophotonics for Peripheral Nerves
Yu Chen, Babak Kateb in Neurophotonics and Brain Mapping, 2017
Another strategy to control neurons is to couple a photoisomerizable molecule (i.e., photoswitch) onto an ordinary ion channel or receptor so that it becomes sensitive to light of different wavelengths (Banghart et al., 2004). The photoswitch is attached in such a way that photoisomerization exerts force on the channel causing it to open. Several chemical photoswitches are available, but azobenzene has emerged as the best one for biological applications (Beharry and Woolley, 2011). In addition to control of neurons, techniques are emerging to read neural activity with light, which include sensing of cell membrane potential, calcium, and neurotransmitter release (Matsuzaki et al., 2001).
Novel approaches to targeted protein degradation technologies in drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Yu Xue, Andrew A. Bolinger, Jia Zhou
In 2019, Carreira’s group reported the first photoswitchable PROTAC [57]. By inducing an ortho-F4-azobenzene linker, they constructed a light-sensitive PROATC, photoPROTAC-1 (38), to realize the light-control degradation of BRD2. The azobenzene moiety acted as a switch to transform 38 into an active azo-trans-isomer upon irradiation at 415 nm, after which the linker length was adjusted to form a stable ternary complex, leading to subsequent BRD2 degradation. Notably, this transformation was reversible. When irradiated at 530 nm, an inactive trans-to-cis transformation occurred, thereby eliminating POI degradation. Furthermore, persistent degradation could be achieved without continuous irradiation due to the bistable nature of the azobenzene switch. Jiang’s group reported Azo-PROTAC-4C (39), which was derived from dasatinib (a BCR-ABL inhibitor) by installing azobenzene onto CRBN ligand [58]. Under 361 nm ultraviolet A (UVA), it induced the degradation of ABL and BCR-ABL in K562 cells, while UVC (200 ~ 280 nm) irradiation caused partial trans-to-cis conversion. Trauner’s group designed a series of photoswitchable PROTACs by engaging azobenzene or diazocine groups onto different attachment sites of published PROTACs (dBET1 and dFKBP-1) [59]. Under irradiation at 390 nm, PHOTAC-I-3 (40) induced degradation of BRD2/3/4 in RS4;11 cells, while PHOTAC-II-5 (41) induced FKBP12 degradation.
Light mediated drug delivery systems: a review
Published in Journal of Drug Targeting, 2022
UV light has been used to influence the contents of amphipathic nano-sized block co-polymers (BCPs) for the sustainable discharge of drugs [23,32,33]. The photoisomerization capability from trans-cis of azobenzene as a part of a BCP is favourable for changes in morphology and subsequently functional properties. A poly (methacrylate) -poly (ethylene oxide)- azobenzene BCP changed its structural moieties when exposed to 365 nm UV illumination [34]. Matyjaszewski's group demonstrated that upon UV irradiation, the polymeric micelle of a BCP was synthesised using a photochromic hydrophobic spiropyran and hydrophilic poly (ethylene oxide) [35]. The micelles formed from an aqueous solution of the BCP were disrupted when illuminated with UV light and subsequently regenerated when visible light was applied to it. The disruption caused by UV light can be a hydrophobic/hydrophilic shift, primary chain degradation, reversible cross-linking, and breakage of block junction [36]. Also, UV light is used in micelles having photocleavable linkers that can be added to the side chain, middle block junction, or form the core of the polymer being used as a carrier. Depending on whether the moieties are hydrophobic, hydrophilic, and, photochromic the substrate can either destabilise partially or disintegrate completely [37,38].
Anticancer nanomedicines harnessing tumor microenvironmental components
Published in Expert Opinion on Drug Delivery, 2022
Yinggang Li, Zhonglan Chen, Lei Gu, Zhengyu Duan, Dayi Pan, Zhuping Xu, Qiyong Gong, Youping Li, Hongyan Zhu, Kui Luo
Khatoon et al. synthesized hypoxic-responsive mesoporous silica nanoparticles with nitroimidazole for rapid drug release. Under a highly reductive environment, the nitroimidazole (Ni) moiety on mesoporous silica nanoparticles changed its hydrophobic state to a hydrophilic one through biological reduction, and nanoparticles disintegrated to release DOX contained in the nanoparticles [77] (Figure 4A). Azobenzene is a promising component for the preparation of hypoxia-responsive NDDSs [78,79]. Yang et al. designed nanoparticles from chlorine 6 (Ce6, a photosensitizer)-conjugated human serum albumin (HSP), oxaliplatin prodrug-conjugated HSP through azobenzene as a covalent bond linker. Under a normal physiological condition, the nanosystems were stable in a round shape with 100–150 nm in size. When they were exposed to a hypoxic tumor microenvironment, reduction of the junction bond of azobenzene resulted in decomposition of the nanosystems into monomers with less than 10 nm in diameter, significantly enhancing intratumoral penetration [80] (Figure 4B).
Related Knowledge Centers
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