The basic technological platform of the company is the design on the basis of peptide and protein compounds, with innovative unified method, of new medical preparations both for the quantitative determination of the respective receptor targets and for the treatment of diseases originating from their dysfunction.
It includes, first of all, the development of peptide highly selective drugs and bringing them to the stage of preclinical trials. An application area of similar preparations can be prophylaxis or treatment of neurodegenerative and psychiatric diseases, cancer, cardiovascular, infectious and some other diseases. In addition, in nearest planes is the development of test-systems for the quantitative determination of the content in the blood or other biological materials of distinct receptor targets – the markers of relevant diseases.
The proposed method is based on the use of the peptide and protein compounds as the starting point for designing new medical products. On the one hand, a unified structural organization of such substances (composed of amino acids) allows us by deleting, adding, or substituting chosen by computer modeling amino acid residues to produce new compounds with desired properties. The peptide origin makes possible a relatively easy preparation of these new compounds by standard methods of solid-phase peptide synthesis. On the other hand, exactly because of more complex structural organization of peptide and protein substances (in contrast to many low molecular weight compounds), they are usually highly selective ligands acting on distinct receptor targets. It guarantees the absence of a broad spectrum of side effects for drugs developed on the basis of peptide compounds.
1. Selection of the initial compounds whose amino acid sequences will be the starting points for designing new analogs with enhanced efficacy and selectivity to distinct receptor targets. Such a choice will be made among the existing peptide-protein «libraries» created in the course of a long natural evolutionary process. The impressive examples of such «libraries» are the venoms of various animal species. In particular, the venoms of snakes contain a large number of structurally and functionally distinguished biologically active proteins and peptides. Another example is the venoms of numerous species of marine mollusks from Conidae family, each of them containing more than 1000 of biologically active peptides. At this stage purification and characterization of novel peptide and protein components from venoms of various species of snakes is carried out.
2. Computer modeling to optimize the structure for a distinct biological target. At this stage the computer simulation procedures are used both for design of novel polypeptide ligands on the basis of initial compounds and for validation of hypotheses on the possible mechanism of their action on respective receptor target. As the initial compounds for designing highly potent and selective to distinct receptors analogs, in addition to purified natural products will be also used synthetic peptides possessing certain biological properties (for example, antimicrobial, antiviral, analgesic, etc.). Modification of their structure may result in an increase or change in the desired direction of their useful properties.
3. Chemical synthesis of analogs or derivatives of the new polypeptide compounds. Employees of the company have a good experience and all technical possibilities for the solid-phase peptide synthesis. The presence of disulfide bonds in the sequences of many neuroactive polypeptides creates some difficulties. However, optimization of methods of synthesis, times and ways of disulfides formation allowed us to produce more than one hundred disulphide-containing peptides in quantities sufficient for biological characterization. The company owns the robotized synthesizer «Syro II» (Germany) which makes possible simultaneous synthesis of 24 products. We have alsoa preparative HPLC system which allows us to purify in a single run a few grams of the raw product.
4. The preparation of photoactivatable, fluorescent and radioactive derivatives of peptide compounds for the structure-functional studies of the respective receptors. The use of such modified ligands allows us to determine the structural features, localization in biological objects and biological activity of the distinct receptor targets. One of the promising directions of this stage could be the creation of test systems for determination of the quantitative level of different receptors with the use of radioactive or fluorescent peptide derivatives.
5. Characterization of biological activity for purified natural or synthesized compounds. The main goal of this stage is determination of the distinct receptor target and a possible mechanism of action for the tested substance. The latter implies the active use of computer modeling methods and verification of derived models by in vitro and in vivo tests. For reliable biological characterization of studied peptide and protein compounds, both the application of different independent biochemical tests and evaluation of their functional (agonist or antagonist) activity are necessary. To determine the binding parameters of tested substances to distinct targets, the radioligand assays will be used. This highly sensitive method (capable to detect 10 femtomoles of receptor) could be used in two variants – namely, as direct and competitive assays. Visualization of interaction of polypeptide compounds or their fluorescently labeled derivatives with natural objects (cells, slices of various organs, etc.) will be carried out by fluorescent microscopy with the use of fluorescent microscope Olympus. Functional activity of the tested substances (blocking of the agonist-induced functional response in the receptor target) will be characterized by electrophysiology methods. It allows researchers to detect the selectivity of the studied compounds in relation to a large number of different receptors.
As a result, the proposed basic technology for designing the medical products on the basis of peptide and protein substances includes the selection of purified and characterized naturally occurring biologically active compounds and design, with application of computer modeling, of their improved analogs capable to target with high efficacy and selectivity distinct receptors. Synthesis of such analogs, their detailed biological characterization and proposed models of the possible mechanism of action through identified targets become the starting point for creation on their basis of test systems and for preclinical trials as new preventive and therapeutic drugs. In the light of current investigations and available patents, applications for patents and scientific publications of the company, the most perspectives is focusing on production of compounds potentially suitable as drugs in the treatment of a number of neurodegenerative, cancer, cardiovascular, infectious and some other diseases.