Patents to synthetic peptides that would act in neuronal diseases

The inventors of these patents granted by the Superintendence of Industry and Commerce (SIC) are the professors Edgar Antonio Reyes Montaño and Nohora Angélica Vega Castro of the National University of Colombia (UNAL), together with Dr. Edwin Alfredo Reyes Guzmán (professor of the Antonio Nariño University) who are part of the Protein Research Group (GRIP) of the UNAL Chemistry Department.


How did you come to this investigation?

The work began as a research project within one of the lines on which the group specializes: the NMDA neuronal receptor, engaged in several neuronal processes and whose alterations in their activities are involved in various pathologies, so that a way to control them through the modulation of the receiver.

"We looked for some proteins or toxins that could interact with this receptor and regulate its functioning," says Professor Reyes, adding that from these we started to design the peptides, initially looking for an antagonistic action, that is, inhibiting the operation of the receiver.

Neurons communicate through neurotransmitters, chemical molecules that send one of these cells to the other. As usually the neurotransmitter can not enter the neuron, at the membrane level it has receptors of that signal to internally generate a series of processes.

In this case, the neurotransmitter is glutamate and the receptor is of the NMDA type: "when the neurotransmitter reaches its receptor it causes channels to open and since neurons basically operate with electricity, it allows ions to enter that modify the electrical charge of the membrane so that the signal can be transmitted, "says the teacher, adding that any change in the amount of charge that is put through the membrane will affect the neuron.

"For example, in diseases such as Parkinson's, Alzheimer's or ischemic processes in cerebrovascular accidents when there is a lack of oxygen, there is a variation in the ionic quantity around the membrane and that is what damages neuronal cells," says Professor Reyes. .

Regulating that step of the amount of ions for the cell to work properly is the function of the NMDA receptor, so that an alteration in its activity can lead to an excess of ions inside or an impediment to the passage of ions; in both cases, the effects are harmful to the cell and on these situations is that the synthetic peptides act.

The idea is that these substances help to restore the regulation of the recipient when it is lost. In one of the patents there are two antagonist peptides, and in the other one that does the opposite effect, which is an agonist, says Professor Reyes.

At the level of pathologies, two of the peptides would be focused on those that cause a lot of calcium to enter, to avoid it, while the third would be indicated for cases in which the receptor does not allow ions to enter, to counteract it.


How did you achieve this achievement?

To produce these synthetic peptides in the laboratory, the researchers took as a reference a conantoquina, a natural toxin that is found in a marine snail and that has properties to interact with the NMDA receptor at an extracellular level, to block its functioning irreversibly.

"The starting point was to take the sequence of that conantoquina and modify some of its amino acids so that it blocked it, but in a reversible way and, in that way, potentiate or diminish the activity of the receptor," says Professor Vega.

These modifications led to the obtaining by bioinformatic methods of a series of 80 peptides that were evaluated; of these, 20 were selected, and finally the three peptides that were patented were selected and evaluated in laboratory tests.

At the moment these peptides can have an immediate application in vitro in the laboratory for tests that require blocking or stimulating the NMDA receptor, instead of using toxins. However, in the future it is expected to apply them to develop therapeutic alternatives in treatment of pathologies that affect the central nervous system mainly.

"The antagonist peptides are already evaluated in an in vitro model of ischemia in which a nerve cell is exposed to a stress in which it will not have oxygen or glucose, which is its main food; that makes her start to activate many things and eventually lead to death, "says Professor Reyes.

In this system, the antagonist peptides were evaluated, showing that they were able to activate neuroprotection processes with which the cells, despite suffering that impact, resisted a little more than those that did not have the peptide.

"Our long-term goal is to generate some drug for these types of disorders that are mediated by a deregulation of this receptor", concludes the teacher.


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