Review of Genetic Variants of Butyrylcholinesterase and Their Potential Impact on Human Health

Butyrylcholinesterase (BChE) is an enzyme found in plasma and many other parts of the body. It is enzyme that hydrolyses drugs containing ester bonds such as drugs acting at the neuromuscular junction (succinylcholine) and local anaesthetics (procaine). Examination of the gene for mutations or polymorphisms causing the observed biochemical phenotypes has isolated those responsible for all the most widely known variants. The molecular bases of several genetic variants of BChE have been reported, such as the Atypical variant, fluoride-resistant variant, silent variant, K variant, J variant and C5 variant. In general, BChE polymorphisms have been shown to produce enzymes with varying levels of catalytic activity. Genetic variants of human butyrylcholinesterase were one of the first examples in the new field of pharmacogenetics when it was recognized that abnormal response to the succinylcholine was due to a mutated enzyme with low binding affinity. Beside that, variant of BChE has potential impact for Alzheimer disease patology.

Genetic diversity in Chrysodeixis includens nucleopolyhedrovirus and factors involved in its generation

In the present thesis, the genetic variability of field-collected isolates of Chrysodeixis includens nucleopolyhedrovirus (ChinNPV) was examined. These results have revealed the great variability present within natural ChinNPV isolates, confirm the differences between two different genetic variants from these isolates and, more important, appear to identify the ChinNPV-K variant as a generator of variability in these isolates. In conclusion, a great variability has been revealed within ChinNPV natural isolates, with a single variant showing a key role in the generation of this diversity in a concentration-dependent manner.

Generation of Variability in Chrysodeixis includens Nucleopolyhedrovirus (ChinNPV): The Role of a Single Variant

The mechanisms generating variability in viruses are diverse. Variability allows baculoviruses to evolve with their host and with changes in their environment. We examined the role of one genetic variant of Chrysodeixis includens nucleopolyhedrovirus (ChinNPV) and its contribution to the variability of the virus under laboratory conditions. A mixture of natural isolates (ChinNPV-Mex1) contained two genetic variants that dominated over other variants in individual larvae that consumed high (ChinNPV-K) and low (ChinNPV-E) concentrations of inoculum. Studies on the ChinNPV-K variant indicated that it was capable of generating novel variation in a concentration-dependent manner. In cell culture, cells inoculated with high concentrations of ChinNPV-K produced OBs with the ChinNPV-K REN profile, whereas a high diversity of ChinNPV variants was recovered following plaque purification of low concentrations of ChinNPV-K virion inoculum. Interestingly, the ChinNPV-K variant could not be recovered from plaques derived from low concentration inocula originating from budded virions or occlusion-derived virions of ChinNPV-K. Genome sequencing revealed marked differences between ChinNPV-K and ChinNPV-E, with high variation in the ChinNPV-K genome, mostly due to single nucleotide polymorphisms. We conclude that ChinNPV-K is an unstable genetic variant that is responsible for generating much of the detected variability in the natural ChinNPV isolates used in this study.

Review of Genetic Variants of Butyrylcholinesterase and Their Potential Impact on Human Health

Butyrylcholinesterase (BChE) is an enzyme found in plasma and many other parts of the body. It is enzyme that hydrolyses drugs containing ester bonds such as drugs acting at the neuromuscular junction (succinylcholine) and local anaesthetics (procaine). Examination of the gene for mutations or polymorphisms causing the observed biochemical phenotypes has isolated those responsible for all the most widely known variants. The molecular bases of several genetic variants of BChE have been reported, such as the Atypical variant, fluoride-resistant variant, silent variant, K variant, J variant and C5 variant. In general, BChE polymorphisms have been shown to produce enzymes with varying levels of catalytic activity. Genetic variants of human butyrylcholinesterase were one of the first examples in the new field of pharmacogenetics when it was recognized that abnormal response to the succinylcholine was due to a mutated enzyme with low binding affinity. Beside that, variant of BChE has potential impact for Alzheimer disease patology.

Review of Genetic Variants of Butyrylcholinesterase and Their Potential Impact on Human Health

Butyrylcholinesterase (BChE) is an enzyme found in plasma and many other parts of the body. It is enzyme that hydrolyses drugs containing ester bonds such as drugs acting at the neuromuscular junction (succinylcholine) and local anaesthetics (procaine). Examination of the gene for mutations or polymorphisms causing the observed biochemical phenotypes has isolated those responsible for all the most widely known variants. The molecular bases of several genetic variants of BChE have been reported, such as the Atypical variant, fluoride-resistant variant, silent variant, K variant, J variant and C5 variant. In general, BChE polymorphisms have been shown to produce enzymes with varying levels of catalytic activity. Genetic variants of human butyrylcholinesterase were one of the first examples in the new field of pharmacogenetics when it was recognized that abnormal response to the succinylcholine was due to a mutated enzyme with low binding affinity. Beside that, variant of BChE has potential impact for Alzheimer disease patology

Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI)

We recently identified the glioblastoma homing peptide CooP (CGLSGLGVA) using in vivo phage display screen. The mammary-derived growth inhibitor (MDGI/FABP3) was identified as its interacting partner. Here, we present an alanine scan of A-CooP to investigate the contribution of each amino acid residue to the binding to FABP3 by microscale thermophoresis (MST) and surface plasmon resonance (SPR). We also tested the binding affinity of the A-CooP-K, KA-CooP, and retro-inverso A-CooP analogues to the recombinant FABP3. According to the MST analysis, A-CooP showed micromolar (KD = 2.18 µM) affinity to FABP3. Alanine replacement of most of the amino acids did not affect peptide affinity to FABP3. The A-CooP-K variant showed superior binding affinity, while A-[Ala5]CooP and A-[Ala7]CooP, both replacing a glycine residue with alanine, showed negligible binding to FABP3. These results were corroborated in vitro and in vivo using glioblastoma models. Both A-CooP-K and A-CooP showed excellent binding in vitro and homing in vivo, while A-[Ala5]CooP and control peptides failed to bind the cells or home to the intracranial glioblastoma xenografts. These results provide insight into the FABP3–A-CooP interaction that may be important for future applications of drug conjugate design and development.