Polyhedral Boron Compounds as Potential Linkers for Attachment of Radiohalogens to Targeting Proteins and Peptides. A Review

2002 ◽  
Vol 67 (7) ◽  
pp. 913-935 ◽  
Author(s):  
Vladimir Tolmachev ◽  
Stefan Sjöberg

Polyhedral boron clusters (PBC) are three-dimensional inorganic aromatic systems. Some of them can easily be halogenated, and the halogen-boron bond in such systems is very strong. We consider the use of PBC as linkers for attachment of radioactive halogen isotopes to tumor-targeting proteins and peptides. In this review the major preconditions for such applications, such as biological considerations, knowledge concerning coupling chemistry and radiolabeling of PBC, are described. A review with 90 references.

2019 ◽  
Vol 9 (2) ◽  
pp. 20180068 ◽  
Author(s):  
Jun Hirabayashi ◽  
Ryoichi Arai

Lectins are a widespread group of sugar-binding proteins occurring in all types of organisms including animals, plants, bacteria, fungi and even viruses. According to a recent report, there are more than 50 lectin scaffolds (∼Pfam), for which three-dimensional structures are known and sugar-binding functions have been confirmed in the literature, which far exceeds our view in the twentieth century (Fujimoto et al. 2014 Methods Mol. Biol. 1200 , 579–606 ( doi:10.1007/978-1-4939-1292-6_46 )). This fact suggests that new lectins will be discovered either by a conventional screening approach or just by chance. It is also expected that new lectin domains including those found in enzymes as carbohydrate-binding modules will be generated in the future through evolution, although this has never been attempted on an experimental level. Based on the current state of the art, various methods of lectin engineering are available, by which lectin specificity and/or stability of a known lectin scaffold can be improved. However, the above observation implies that any protein scaffold, including those that have never been described as lectins, may be modified to acquire a sugar-binding function. In this review, possible approaches to confer sugar-binding properties on synthetic proteins and peptides are described.


2017 ◽  
Vol 14 (136) ◽  
pp. 20170423 ◽  
Author(s):  
David Pulido ◽  
Rocío Rebollido-Rios ◽  
Javier Valle ◽  
David Andreu ◽  
Ester Boix ◽  
...  

Lipopolysaccharides (LPSs) and glycosaminoglycans (GAGs) are polymeric structures containing negatively charged disaccharide units that bind to specialized proteins and peptides in the human body and control fundamental processes such as inflammation and coagulation. Surprisingly, some proteins can bind both LPSs and GAGs with high affinity, suggesting that a cross-communication between these two pathways can occur. Here, we explore whether GAGs and LPSs can share common binding sites in proteins and what are the structural determinants of this binding. We found that the LPS-binding peptide YI12WF, derived from protein FhuA, can bind both heparin and E. coli LPS with high affinity. Most interestingly, mutations decreasing heparin binding in the peptide also reduce LPS affinity. We show that such mutations involve the CPC clip motif in the peptide, a small three-dimensional signature required for heparin binding. Overall, we conclude that negatively charged polysaccharide-containing polymers such as GAGs and LPSs can compete for similar binding sites in proteins, and that the CPC clip motif is essential to bind both ligands. Our results provide a structural framework to explain why these polymers can cross-interact with the same proteins and peptides and thus contribute to the regulation of apparently unrelated processes in the body.


2009 ◽  
Vol 60 (5) ◽  
pp. 285-288 ◽  
Author(s):  
O COJOCARUMIREDIN ◽  
E CADEL ◽  
F VURPILLOT ◽  
D MANGELINCK ◽  
D BLAVETTE

2005 ◽  
Vol 1 (4) ◽  
pp. 259-270 ◽  
Author(s):  
Kah Chun Lau ◽  
Ravindra Pandey

The rich chemistry of boron compounds are often found dominated by its structural dimensionality and chemical bonding from which some of the qualitative features of boron clusters can easily be extracted. In this article, we review such features to discuss structural properties of Bn clusters. In both small-cluster regime of n ≤ 20 and largecluster regime of n ≥ 20, the preferred topological structures are the result of the interplay between bonding factors related to the delocalized π bonds and the inter-icosahedral and intra-icosahedral bonds. The bulk fragments of boron are also expected to become a competitive isomeric configuration with the increase in the cluster-size, in contrast to 3D spherical cages observed in the large carbon clusters


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hisatsugu Yamada ◽  
Natsuki Matsumoto ◽  
Takanori Komaki ◽  
Hiroaki Konishi ◽  
Yu Kimura ◽  
...  

Abstract Three-dimensional (3D) representation of a tumor with respect to its size, shape, location, and boundaries is still a challenge in photoacoustic (PA) imaging using artificial contrast agents as probes. We carried out PA imaging of tumors in mice using 800RS-PMPC, which was obtained by coupling of 800RS, a near-infrared cyanine dye, with PMPC, a highly selective tumor-targeting methacrylate polymer having phosphorylcholine side chains, as a probe. The conjugate 800RS-PMPC forms compact nanoparticles (dDLS = 14.3 nm), retains the biocompatibility of the parent polymer (PMPC) and exhibits unprecedented PA performance. When applied to mice bearing a 6 × 3 × 3 mm3 tumor buried 6 mm beneath the skin, the probe 800RS-PMPC selectively accumulates in the tumor and emits PA signals that are strong enough to be unambiguously distinguished from noise signals of endogenous blood/hemoglobin. The PA image thus obtained under high-threshold conditions allows 3D characterization of the tumor in terms of its size, shape, location, and boundaries.


Science ◽  
2021 ◽  
Vol 371 (6536) ◽  
pp. 1338-1345 ◽  
Author(s):  
Jiajia Ma ◽  
Shuming Chen ◽  
Peter Bellotti ◽  
Renyu Guo ◽  
Felix Schäfer ◽  
...  

Dearomative cycloaddition reactions represent an ideal means of converting flat arenes into three-dimensional architectures of increasing interest in medicinal chemistry. Quinolines, isoquinolines, and quinazolines, despite containing latent diene and alkene subunits, are scarcely applied in cycloaddition reactions because of the inherent low reactivity of aromatic systems and selectivity challenges. Here, we disclose an energy transfer–mediated, highly regio- and diastereoselective intermolecular [4 + 2] dearomative cycloaddition reaction of these bicyclic azaarenes with a plethora of electronically diverse alkenes. This approach bypasses the general reactivity and selectivity issues, thereby providing various bridged polycycles that previously have been inaccessible or required elaborate synthetic efforts. Computational studies with density functional theory elucidate the mechanism and origins of the observed regio- and diastereoselectivities.


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