Bio-Implants Derived from Biocompatible and Biodegradable Biopolymeric Materials
P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas in Advanced Studies in Experimental and Clinical Medicine, 2021
Cooper et al. [13] have developed polymers with high molecular weights. It also gives high tensile properties and melts processability similar to synthetic polymers. Hence can be used as similar as radiation sterilizable aromatic polyanhydride. Nicholas et al. [6] have developed a new route for the preparation of fluorescent bioconjugates by living radical polymerization using protein-derived macro initiators. These fluorescent bioconjugates can be easily traceable in biological environments, during biomedical assays. Cycloaddition reactions have been explored by Grayson et al. [14] to prepare macrocyclic poly(hydroxyl styrene). The presence of a phenolic hydroxyl group on each repeat unit in the cyclic polymer gives better scope for attachment of bioactive counterparts. The cyclization technique to have a wider application for preparing a wide range of functionalized macrocycles. Smith and coworkers [15] found poly(N-vinylpyrrolidinone) hydrogels functionalized with drug molecules as promising hydrogels for sustained release of drugs over several days.
Laccase-Mediated Synthesis of Novel Antibiotics and Amino Acid Derivatives
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
The radical may then undergo formation of a quinoid derivative (Manda et al., 2007), or intermolecular nucleophilic attack to produce homomolecular dimers (Fig. 8.2; Tables 8.1a and 8.1b). Formation of homomolecular and heteromolecular dimers (simplified structure); R = several substituents or ring systems presented with examples in Tables 8.1a and 8.1b: (1) Reaction type = oxidative coupling, oxidative condensation or phenolic oxidative coupling. (2) Reaction type = oxidation coupled with nuclear amination. (3) Reaction type = oxidation coupled with cyclization.
Nucleic Acids as Therapeutic Targets and Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
The enediynes (Figure 5.57) are a class of bacterial natural products characterized by either nine- or ten-membered rings containing two triple bonds separated by a double bond. These compounds are capable of undergoing a unique internal chemical reaction known as the Bergman cyclization. The resulting di-radical formed, a 1,4-dehydrobenzene species, is capable of abstracting hydrogen atoms from the sugar backbone of DNA. This results in double-strand breaks in the double helix which are problematic for the cell to repair, thus rendering the compounds extremely cytotoxic. Examples of structures of the enediyne family of DNA-cleaving bacterial natural products: Neocarzinostatin, Calicheamicin γ1, Esperimicin. and Dynemicin A.
Elucidating the structure and cytochrome P450-mediated mechanism for novel metabolites of GDC-0575 in rats
Published in Xenobiotica, 2022
Chenghong Zhang, Sungjoon Cho, José G. Napolitano, David Russell, Christine Gu, Alan Deese, Chong Han, Yuan Chen, Shuguang Ma
Several studies reported similar cases of CYP-mediated cyclisation or dimerisation reactions. Gu et al reported similar oxidation-mediated cyclisation from AZD7325 where hydroxylation led to subsequent formation of imine which was attacked by free amine to generate the cyclized metabolite (Gu et al. 2018). It is reported that CYP mediates two distinct cyclized metabolites from GDC-0623 through (1) N-N bond formation between the aniline and hydroxamate or (2) Hofmann-type rearrangement involving C-C bond cleavage and C-N bond formation (Takahashi et al. 2015). CYP3A4 and 3A5 mediated the dimerisation of GDC-0994 via radical coupling (Takahashi et al. 2020). Gillam et al. reported the oxidation of indole by P450 to indoxyl, which was subsequently oxidised and dimerised to form indigoids (Gillam et al. 2000). Homodimerization of raloxifene was also reported to occur via a CYP3A4-mediated oxidative reaction (Davis et al. 2011). To our knowledge, this is the first case that CYP-mediated oxidation leading to the formation of both cyclized and subsequent dimer metabolites.
Antimicrobial peptides and other peptide-like therapeutics as promising candidates to combat SARS-CoV-2
Published in Expert Review of Anti-infective Therapy, 2021
Masoumeh Sadat Mousavi Maleki, Mosayeb Rostamian, Hamid Madanchi
Peptidomimetics are designed based on small protein-like chains or small molecules that mimic the behavior of a peptide and have regulated molecular properties, such as high stability or biological activity. The use of peptidomimetics is a very powerful strategy for designing small molecule-based drugs as enzyme inhibitors or receptor ligands [106]. These compounds mimic a natural peptide or a protein of the viruses and have the ability to interact with their biological targets and produce the same biological effects [107]. There are different types of changes to create peptidomimetics with improved drug properties, including local changes, such as the binding of nonstandard amino acids, and general changes, such as forming a circular end in polypeptide chains during a cyclization process. Cyclization is one of the most common strategies used to convert peptides into drugs and pharmacologically active agents [108].
RGD peptide-based non-viral gene delivery vectors targeting integrin αvβ3 for cancer therapy
Published in Journal of Drug Targeting, 2019
Shuang Fu, Xiaodong Xu, Yu Ma, Shubiao Zhang, Shufen Zhang
The ultimate efficacy of RGD will be likely influenced by many factors, such as steric conformation, direct interaction between additional flanking groups, their receptors and so on [27,28]. Many different RGD-containing peptides with variable structures and flanking amino acids have been examined for a better understanding of RGD activity in vitro and in vivo. The identity of flanking sequence is known to alter both the adhesive strength of RGD as well as selectivity for distinct integrin heterodimers [29–35]. In fact, the cyclisation which confers rigidity to the structure is commonly employed to improve the binding properties of RGD peptide. Furthermore, linear RGD peptide was proved highly susceptible to chemical degradation, which is due to the reaction of the aspartic acid residue (D) with the peptide backbone [36]. Since the rigidity conferred by cyclisation prevents chemical degradation, cyclic peptides are more stable, more potent and more specific. The RGD peptide sequence is flanked by other amino acids in cyclic peptide to build a ring system. These systems offer the possibility to present the RGD sequence in a specific conformation for a selected integrin [28].
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