Laboratory of hormonal regulation proteins

Department of Peptide and Protein Technologies

Head: Valery Lipkin, corresponding member of the academy of sciences
vmlipkin@ibch.ru+7(495)336-61-66

Proteins, peptides, differentiation, apoptosis, Alzheimer’s disease, ischemia, myopia

The Laboratory researches the proteins including in transmembrane signaling processes, differentiation and cell apoptosis, and also new proteins and peptides associated with the pathogenesis of social diseases. As a result researchers develop new approaches for the treatment and diagnosis of these diseases. In addition, the Laboratory develops methods of genotyping used in agriculture.

The Laboratory have discovered and studied a new factor of differentiation of blood cells (HLDF) which suppress the proliferation of promyelocytic leukemia cell lines. In six-membered HLDF-peptide 6 (TGENHR) factor was identified composition having nootropic and neuroprotective activity. During successful preclinical testing in animal models of clinical disease (Alzheimer's disease and ischemic stroke) Anne Bogachuk’s Group showed that protected by amidation at the C-terminal carboxyl group of the peptide form (HLDF-6-NH2) considerably exceeds the activity of the peptide original shape almost completely restores impaired cognitive function and does not cause some toxic effects and can be recommended for further clinical studies.

The attention of researchers was drawn by another neurotrophic factor – PEDF (Pigment Epithelium Derived Factor), which accumulates with myopia and promotes the formation of amyloid fibrillar structures. This knowledge opens new approaches to the treatment of eye diseases widespread.

Researchers conduct studies laboratory EIF1AD protein (gaponina) which was opened in the Laboratory and regulates the processes in the body related to oxidative stress (OS). EIF1AD localized in the nucleus and controls the transcriptional activity of p53 protein, caused by reactive oxygen species. The suppression of EIF1AD expression via shRNK inhibits apoptosis induced by the OS and promotes cell survival, such as ultraviolet, gamma irradiation or during inflammation.

Tatiana Shuvaeva’s Group develops methods for genotyping of cattle for identification of genetic diseases and the further improvement of breed herds.

Laboratory cooperates with laboratories of the Institute, as well as with The Anokhin Institute of Normal Physiology RAS, The Zakusov Institute of Pharmacology, The Institute of Cell Biophysics RAS, The Institute of Molecular Genetics RAS, The Helmholtz Moscow Research Institute of Eye Diseases of the Russian Ministry of Health, People’s Friendship University of Russia, The Kuban State Agrarian University, Department of Medical Biochemistry and Biophysics of Umeå University (Sweden) etc.

The Laboratory was formed in 1986 on the basis of the group existing from 1975 in the Department of protein chemistry, heading by academician Yu.A. Ovchinnikov.

  1. Physico-chemical biology;
  2. Investigations of structure and functioning mechanism of proteins and peptides, participating in transmembrane signal transduction, cells differentiation and apoptosis;
  3. Elaboration of new preparations for cancer and neurodegenerative diseases therapy, regeneration of human damaged tissues and organs.

The Laboratory was formed in 1986 on the basis of the group existing from 1975 in the Department of protein chemistry, heading by academician Yu.A. Ovchinnikov.

1986—1997. Primary structure of all subunits of bovine and human cGMP phosphodiesterase was estimated. Using immunochemical methods and site-directed mutagenesis, in photoreceptor cGMP phosphodiesterase, functional amino acid residues were localized and mechanisms of photoactivation and inhibition of the enzyme were elucidated. In 1997, the work was awarded by Yu.A. Ovchinnikov prize.

1996—2008. Two new secretory proteins with molecular weights 28 and 45 kDa were isolated from the rat’s olfactory epithelium. Their complete amino acid sequences were determined. 28 kDa protein has been identified as peroxyredoxin VI. It was shown to act as antioxidant and might be used as a novel remedy, promoting regeneration of damaged human tissues and organs (in cooperation with the Institute of the Cell Biophysics RAS). In the structure of 45 kDa protein, a lipid-binding domain was identified. The protein was ascertained to belong to lipid-transferring class, and phosphatydilinositol-(3,4,5)-triphosphate is its specific ligand.

2006—2008. In the HL-60 cell line of human promyelocytic leukemia, a new protein was discovered with molecular mass 19,2 kDa, named haponin (HLDF-alike protein), immunoreactive with polyclonal antibodies to one of HLDF analogs (HLDFβ). Full-sized cDNA of haponin was cloned, and its structure was determined. We suppose participation short form of haponin (molecular mass. kDa) in normal apoptosis of lymphoid tissue.

2006—2014. Else one line of investigation in the Laboratory is connected with study of functional role of neurotrophic factor from pigment epithelium PEDF (Pigment Epithelium Derived Factor) on myopia progression. We have recently shown, that normal PEDF factor, secreted by sclera phibroblasts, undergoes partial proteolysis by 382Leu-383Тhr bond that results in removal of C-terminal fragment. At myopia this process is disturbed that gives rise to accumulation in pericellular space of full-size PEDF, able to form amyloid—like fibrillary structures, decreasing biomechanical stability of sclera tissues. We suppose that using of the substances preventing fibrils formation would permit to stop myopia progression.

20122015. Preclinical studies of HLDF-peptide 6 were conducted to developing a medicament for the prevention and treatment of neurodegenerative (Alzheimer's disease) or cerebrovascular (ischemic stroke) diseases. The most active form of HLDF-6 peptide having neuroprotective and nootropic activity was identified. In the comparative study of the activity of the parent peptide and the peptide protected from protease action with the C-terminus amide group was found that the peptide protected form in all investigated animal models of ischemic stroke and Alzheimer's disease almost completely restores impaired cognitive function, efficiency exceeding the parent peptide. The study of acute, sub-chronic and chronic toxicity, allergenicity, mutagenicity and mechanism of the peptide amide form action was conducted.

The conclusion was made on the basis of the study that the drug, based on the peptide HLDF-6 amide form with repeated intranasal administration to male and female rats does not cause toxic effects and is safe. The drug based on the peptide HLDF-6 amide form at a dose of 5000 mg / kg does not cause toxic effects, it complies with the requirements of the low hazard class 4 "low-hazard substances" and could be recommended for further research. The advantages of our product over other existing drugs determined by the aggregate of such medicinal properties as originality, expression of therapeutic effect, a high level and wide range of combined nootropic and neuroprotective activity (effective influence on both diseases - asthma and ischemic stroke), high efficiency in small and ultralow doses, no undesirable side effects.

NamePositionContacts
Valery Lipkin, corresponding member of the academy of sciencesdepart. dir.vmlipkin@ibch.ru+7(495)336-61-66
Tat'jana Shuvaeva, D.Scl. r. f.shuvaeva@mx.ibch.ru+7(495)336-51-11
Anna Bogachuk, Ph.D.s. r. f.apbogachouk@gmail.com+7(495)336-51-11
Tat'jana Rakitina, Ph.D.s. r. f.taniarakitina@yahoo.com+7(495)330-63-47
Dmitrij Kakuevr. f.dkakuev@mail.ru+7(495)330-63-47
Vitaly Radchenko, Ph.D.r. f.vitalyradchenko@yandex.ru+7(495)336-55-11
Elena Surinar. f.surinae@mx.ibch.ru+7(495)336-55-11
Elena Il'nitskaya, Ph.D.r. f.nevrilemma@yandex.ru+7(495)335-26-00
Evgenia Smirnova, Ph.D.r. f.smirnova.evgeniya@gmail.com+7(495)330-63-47
Natal'ja Minkevich, Ph.D.j. r. f.ni-minkevich@gmail.com+7(495)336-55-11
Elena Vorob'evaPhD stud.e-elena777@yandex.ru
Anastasia Frolovat. q. - lab. as.
Irina Smirnovares. eng.smirnova@mx.ibch.ru+7(495)336-55-11

Former members:

Igor' Artamonov, Ph.D.s. r. f.
Irina Kostanjan, Ph.D.s. r. f.
Alexey Garkovenkoj. r. f.garkovenko@gmail.com

Selected publications (show all)

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Valery Lipkin

  • Russia, Moscow, Ul. Miklukho-Maklaya 16/10 — On the map
  • IBCh RAS, build. ФИБХ, office. БОН/203
  • Phone: +7(4967)79-39-71
  • E-mail: vmlipkin@ibch.ru

Neuroprotective activity of HLDF-6 peptide was shown on double- transgene model of Alzheimer’s disease (2017-12-15)

Neuroprotective and nootropic activities of amide form (AF) of HLDF-6 peptide (TGENHR-NH2) were studied on transgene mice of B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) line – animal model of inherited Alzheimer’s disease. Animals of this line express the mutant human presenilin and chimeric mouse/human amyloid protein. A typical feature of this line is early development of an Alzheimer-like pathology caused by accelerated βA deposition and cognitive impairment in the brain, which is evaluated using the spatial learning tests. The cognitive abilities of B6C3-Tg-  have not been fully characterized.