Chapter 20 ω-Conotoxins and Voltage-Sensitive Calcium Channel Subtypes

Cruz, Lourdes J.; Johnson, D. S.; Imperial, Julita S.; Griffin, David C.; LeCheminant, Garth W.; Miljanich, George P.; Olivera, Baldomero M.

doi:10.1016/s0070-2161(08)60910-7

Cited by 13 publications

(2 citation statements)

References 27 publications

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“…In 1985, Olivera sent a calcium channel blocker, conopeptide, to George Miljanich, who wanted to test ω-conotoxins for his work on neurotransmitter release at the University of Southern California and, three years later, they published a book chapter together [ 6 ]. Miljanich continued the ω-conotoxins research [ 7 , 8 ] and the progression from pharmacological tools for basic neuroscience to a therapeutic candidate can be credited to him [ 9 ] since he was recruited by a private biotech start-up company called Neurex (Menlo Park, CA, USA) in 1988 and even when ω-conotoxins were initially considered useful as neuroprotective in animal models of stroke [ 10 ], Miljanich showed that they were potent, specific, and degradation resistant, making them perfect to become pharmaceutical compounds for pathological pain [ 11 , 12 , 13 , 14 , 15 , 16 ].…”

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confidence: 99%

Conotoxin Patenting Trends in Academia and Industry

2022

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Sea snails of the genus Conus produce toxins that have been the subjects of numerous studies, projects, publications, and patents over the years. Since Conus toxins were discovered in the 1960s, their biological activity has been thought to have high pharmaceutical potential that could be explored beyond the limits of academic laboratories. We reviewed 224 patent documents related to conotoxins and conopeptides globally to determine the course that innovation and development has taken over the years, their primary applications, the technological trends over the last six years, and the leaders in the field, since the only previous patent review was performed in 2015 and focused in USA valid patents. In addition, we explored which countries/territories protect their inventions and patents and the most relevant collaborations among assignees. We also evaluated whether academia or pharmaceutical companies are the future of conotoxin research. We concluded that the 224 conotoxin patents reviewed in this study have more academic value than industrial value, which was noted by the number of active patents that have not yet been licensed and the contributions to medical research, especially as tools to study neuropathic pain, inflammation, immunology, drug design, receptor binding sites, cancer, neurotransmission, epilepsy, peptide biosynthesis, and depression. The aim of this review is to provide an overview of the current state of conotoxin patents, their main applications, and success based on the number of licensing and products in the market.

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Section: Introductionmentioning

confidence: 99%

Conotoxin Patenting Trends in Academia and Industry

2022

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“…Initial functional studies indicated that -CgTx GVIA is a potent, irreversible blocker of a subclass of VDCC as defined by its species-and tissuedependent blockade (Cruz & Olivera, 1986;Reynolds et al, 1986;Cruz et al, 1987;McCleskey et al, 1987;Kasai et al, 1987;Suszkiw et al, 1987). Specifically, -CgTx GVIA selectively interacts with neuronal versus nonneuronal VDCC and preferentially blocks the influx of Ca2+ into avian, amphibian, and fish nerve terminals versus mammalian nerve terminals [for a review, see Cruz et al (1988)]. Within mammalian tissues, both peripheral and central nerve terminals contain -CgTx GVIA-sensitive sites as demonstrated by the potent blockade of norepinephrine release from rat sympathetic neurons (Hirning et al, 1988) and from rat brain slices (Dooley et al, 1987;Keith et al, 1989).…”

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Effects of site-specific acetylation on .omega.-conotoxin GVIA binding and function

Lampe

Lo²,

Keith³

et al. 1993

Biochemistry

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Chemical modification of omega-conotoxin GVIA (omega-CgTXGVIA) was performed using nonsaturating concentrations of acetic anhydride to generate seven distinct derivatives. Following separation of these peptides using reverse-phase HPLC (RP-HPLC), their individual molecular weights were determined using fast bombardment mass spectrometry (FAB-MS). Three peptides contained a single acetylated amino group, three possessed two acetylated amino groups, and the last contained three acetylations. For each peptide, the specific site of acetylation was confirmed using a scheme of tryptic digestion, under nonreducing conditions, followed by RP-HPLC and FAB-MS. Biological profiles for each peptide were obtained by analyzing their capacity to displace native 125I-omega-CgTx GVIA binding to rat hippocampal membranes and to block K(+)-stimulated 45Ca2+ influx into chick brain synaptosomes. The data indicate that successive additions of acetyl moieties to omega-CgTx GVIA lead to a loss of both binding affinity and Ca2+ influx inhibitory potency. Within the monoacetylated series, acetylation of the amino terminal of Cys-1, as compared to the epsilon-amino group of either Lys-2 or Lys-24, leads to the greatest shift in potency. In summary, these results indicate that basic (i.e., primary amino) groups, which are brought into close proximity as a result of disulfide bridging, are important in the functional blockade of neuronal Ca2+ channels by omega-CgTx GVIA.

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