Novel platform for the preparation of synthetic orally active peptidomimetics with hemoregulating activity. II. Hemosuppressor activity of 2,5-diketopiperazine-based cyclopeptides

Q2 · MEDICINE

Article

Author: Yatskin, Oleg ; Feofanov, Alexey ; Ignatova, Anastasia ; Ksenofontova, Olga ; Goryacheva, Alexandra ; Ivanov, Vadim ; Deigin, Vladislav

The novel chemical platform formed by the branched piperazine-2,5-dione peptide derivatives (2,5-diketopiperazines) for creating non-invasive biologically active peptidomimetics has been developed. A successful application of this approach to orally available hemostimulatory peptidomimetics was demonstrated for all-L cyclopeptide from the Glu-Trp-peptide family. In the 1980s, we have separated and characterized a number of dipeptides from the thymus homogenate. The most active peptide Glu-Trp has been studied and developed into the immunostimulating drug Thymogen. The inversion of the amino acid optical form endows the dipeptides with suppressor properties: D-Glu-D-Trp-OH and D-Glu-(D-Trp)-OH, inhibit proliferation of hemopoietic progenitors in the intact bone marrow. Based on the peptide D-Glu-(D-Trp)-OH, the new immunosuppressive drug Thymodepressin has been prepared. In this work, we applied the platform mentioned above to the design and synthesis of orally active hemosuppressive Thymodepressin® analogs. The novel data for the hemosuppressor activity of the dipeptide D-Glu(D-Trp-OH)-OH and its cyclopeptide analogs are discussed. A new example is presented of a rare phenomenon when enantiomeric molecules demonstrate reciprocal (i.e., opposite) biological activities.

01 Apr 2011·Bulletin of Experimental Biology and MedicineQ4 · MEDICINE

Status of Free-Radical Oxidation and Proliferation Processes in Patients with Atopic Dermatitis and Lichen Planus

Q4 · MEDICINE

Article

Author: Lebed'ko, O. A. ; Sapuntsova, S. G. ; Kozulin, E. A. ; Fleyshman, M. Yu. ; Timoshin, S. S. ; Shchetkina, M. V.

We studied the status of proliferation processes (by Ki-67 expression) and biogenesis of free radicals (by chemiluminescence method) in skin biopsy specimens from patients with atopic dermatitis and lichen planus. The index of Ki-67-positive nuclei significantly (p<0.05) increased to 28.40±2.00% in patients with dermatitis and to 32.6±1.9% in patients with lichen planus vs. 8.65±1.31% in the reference sample. Decompensated accumulation of free-radical oxidation products and inhibition of detoxification systems in skin biopsy specimens indicate the development of local oxidative stress. After therapy consisting of two 10-day courses of thymodepressin injections (0.1%, 1.0 ml) over 30 days, normalization of epidermis proliferation was observed. Labeling index in atopic dermatitis and lichen planus significantly decreased (p<0.05) to 17.00±1.87 and 10.9±1.1%, respectively. The role of free radicals in the development of hyperregeneratory processes during dermatoses is discussed.

01 Jul 2008·Bulletin of Experimental Biology and MedicineQ4 · MEDICINE

Dipeptide γ-d-Glu-d-Trp (thymodepressin) inhibits migration of Cd34+ cells from the bone marrow into peripheral blood during tumor growth

Q4 · MEDICINE

Article

Author: Iljina, T. P. ; Semenets, T. N. ; Semina, O. V. ; Semin, D. Yu. ; Selivanova, E. I. ; Maliutina, Ya. V. ; Zamulaeva, I. A. ; Deigin, V. I. ; Saenko, A. S.

We studied the effect of dipeptide gamma-d-Glu-d-Trp (thymodepressin) on migration of CD34+ hemopoietic precursors and their direct adhesion to fibronectin in tumor-bearing mice on days 8, 11, 15, and 17 of tumor growth and on expression of CXCR-4 (CD184+) to SDF-1 and integrin beta1 (CD29+) by bone marrow cells. In tumor-bearing mice treated with gamma-d-Glu-d-Trp, the percent of CD34+ hemopoietic precursors in the peripheral blood considerably decreased throughout the observation period; the content of CD34+ hemopoietic precursors in the tumor tissue was 2-3-fold below the control against the background of increased content of CD34+ cells in the bone marrow. In animals treated with the peptide, the content of cells expressing CXCR-4 in the peripheral blood, bone marrow, and tumor tissue significantly decreased, while the percent of cells expressing integrin beta1 receptor (CD29+) in the bone marrow increased 2-fold, which was paralleled by an almost 2-fold increase in the percent of cells binding to fibronectin. We hypothesized that dipeptide gamma-d-Glu-d-Trp suppressed mobilization/migration of CD34+ hemopoietic precursor cells from the bone marrow to the peripheral blood of tumor-bearing mice.

100 Deals associated with Disodium D-glutamyl L-tryptophan(Pharma Bio Llc)

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Indication	Country/Location	Organization	Date
Autoimmune Diseases	RU	Apogee Bio-Pharm LLC	26 Oct 2010
Graft Rejection	RU	Apogee Bio-Pharm LLC	26 Oct 2010
Hematologic Diseases	RU	Apogee Bio-Pharm LLC	26 Oct 2010
Chemotherapy-induced damage	RU	Apogee Bio-Pharm LLC	14 Oct 2010

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