RESUMEN
Peptide CH3CO-Lys-Lys-Arg-Arg-NH2 (protectin) was synthesized and its activity was studied on the model of experimental myocardial infarction in rats in comparison to the reference antihypoxant drug riboxin. Intranasal injections ofprotectin at doses within 2-20 microg/kg once a day by course of 7 days produced a pronounced anti-ischemic action, improved coronary circulation of the blood, increases contractile activity of myocardium, reduced intensity of lipid peroxidation, and improved antioxidant protection. In some respects (improved coronary circulation of the blood, increased antioxidant protection), protectin was more effective than riboxin.
Asunto(s)
Inosina Difosfato/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Oligopéptidos , Administración Intranasal , Animales , Antioxidantes/metabolismo , Circulación Coronaria/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Peroxidación de Lípido/efectos de los fármacos , Masculino , Oligopéptidos/administración & dosificación , Oligopéptidos/síntesis química , Ratas , Ratas Sprague-DawleyRESUMEN
Research results of the synthetic decapeptide SLTCLVKGFY (the author's term is immunorphin) corresponding to the 364-373 sequence of G heavy-chain human immunoglobulin are summarized. Special attention is paid to the interaction between immunorphin and a nonopioid (insensitive to the opioid antagonist naloxone) beta-endorphin receptor. Using radioligand analysis, data were found regarding the distribution and functions of a nonopioid beta-endorphin receptor in human and animal bodies and the binding characteristics of immunorphin with a nonopioid receptor.
Asunto(s)
Regiones Constantes de Inmunoglobulina/farmacología , Cadenas gamma de Inmunoglobulina/farmacología , Oligopéptidos/farmacología , Fragmentos de Péptidos/farmacología , Receptores de Péptidos/metabolismo , betaendorfina/metabolismo , Secuencia de Aminoácidos , Animales , Desarrollo Embrionario/efectos de los fármacos , Humanos , Datos de Secuencia Molecular , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Especificidad de Órganos , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , betaendorfina/farmacologíaRESUMEN
We have synthesized the peptide TPLVTLFK corresponding to the ß-endorphin fragment 12-19 (the name given by the authors - octarphin), and its analogs (LPLVTLFK, TLLVTLFK, TPLVLLFK, TPLVTLLK, TPLVTLFL). The peptide octarphin was labeled with tritium (the specific activity of 28 Ci/mmol) and its binding to the murine peritoneal macrophages has been studied. [(3)H]Octarphin was found to bind to macrophages with high affinity (K(d) = 2.3 ± 0.2 nM) and specificity. The specific binding of [(3)H]octarphin is inhibited by unlabeled ß-endorphin and selective agonist of non-opioid ß-endorphin receptor synthetic peptide immunorphin (SLTCLVKGFY) (K(i) = 2.7 ± 0.2 and 2.4 ± 0.2 nM respectively) and not inhibited by unlabeled naloxone, α-endorphin, γ-endorphin and [Met(5)]enkephalin (K(i) > 10 µM). Inhibiting activity of unlabeled analogs of octarphin is more then 100 times lower the unlabeled octarphin. Octarphin stimulates activity of murine immunocompetent cells in vitro and in vivo: at the concentration of 1-10 nM enhances the adhesion and spreading of peritoneal macrophages as well as their capacity to digest bacteria of Salmonella typhimurium virulent strain 415 in vitro. Intraperitoneal administration of peptide at dose 20 µg/animal on day 7,3 and 1 prior to the isolation of cells increases activity of peritoneal macrophages as well as T- and B-spleen lymphocytes.
Asunto(s)
Macrófagos Peritoneales/efectos de los fármacos , Oligopéptidos/farmacología , Fragmentos de Péptidos/farmacología , Receptores Opioides/metabolismo , betaendorfina/farmacología , Secuencia de Aminoácidos , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Adhesión Celular/efectos de los fármacos , Células Cultivadas , Regiones Constantes de Inmunoglobulina/química , Regiones Constantes de Inmunoglobulina/farmacología , Cadenas gamma de Inmunoglobulina/química , Cadenas gamma de Inmunoglobulina/farmacología , Ligandos , Activación de Linfocitos/efectos de los fármacos , Macrófagos Peritoneales/fisiología , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Oligopéptidos/síntesis química , Oligopéptidos/química , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/química , Fagocitosis/efectos de los fármacos , Unión Proteica , Ensayo de Unión Radioligante , Bazo/efectos de los fármacos , Bazo/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , betaendorfina/síntesis química , betaendorfina/químicaRESUMEN
The CH3CO-Lys-Lys-Arg-Arg-NH2 peptide (the author has named it protectin) was synthesized, and its activity was studied during different stress actions. Protectin was found to normalize the content of corticosterone and adrenalin in adrenal glands and blood after its intranasal administration to rats one day before a cold or heat shock, or hypobaric hypoxia at doses of 1-10 microg/animal and after its intravenous administration just after acute hemorrhage at doses of 0.5-2 microg/animal. The intranasal administration of protectin at doses of 1-10 microg/rat one day before the heat or cold shock was also shown to prevent a change in the content of free histamine and the activity of diamine oxidase in myocardium, which was induced by the dramatic change in the activity of the enzyme after the temperature actions.
Asunto(s)
Síndrome de Adaptación General/prevención & control , Oligopéptidos/uso terapéutico , Sustancias Protectoras/uso terapéutico , Estrés Fisiológico/efectos de los fármacos , Administración Intranasal , Corteza Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/metabolismo , Amina Oxidasa (conteniendo Cobre)/metabolismo , Animales , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Corticosterona/sangre , Epinefrina/sangre , Síndrome de Adaptación General/sangre , Síndrome de Adaptación General/enzimología , Síndrome de Adaptación General/metabolismo , Histamina/metabolismo , Masculino , Miocardio/enzimología , Miocardio/metabolismo , Oligopéptidos/síntesis química , Oligopéptidos/química , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/síntesis química , Sustancias Protectoras/química , Ratas , Ratas Sprague-DawleyRESUMEN
The activity of the KKRR synthetic peptide corresponding to the 15-18 sequence of human adrenocorticotropic hormone (ACTH) and its analogues KKKK, RRRR, RRKK, kKRR, KkRR, KKrR, and KKRr (amino acid residues of the D configuration are designated by small letters) was studied in vivo on rats under cold and heat shock. Intranasal administration of the KKRR peptide at doses of 2-10 microg/animal 1 day before the shock was found to prevent a dramatic increase in the level of corticosterone in rat adrenal glands and blood plasma caused by the temperature effect. Amino acid substitutions in the KKRR peptide were shown to result in an abrupt decrease in its activity. The peptide analogues exhibit a low stress-protective activity and had a low affinity for the ACTH receptor.
Asunto(s)
Hormona Adrenocorticotrópica/farmacología , Corticosterona/metabolismo , Péptidos/farmacología , Estrés Fisiológico/fisiología , Animales , Frío/efectos adversos , Corticosterona/sangre , Calor/efectos adversos , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Fragmentos de Péptidos/farmacología , Ratas , Ratas Sprague-Dawley , Estrés Fisiológico/efectos de los fármacosRESUMEN
The tritium-labeled dipeptide bestim (gamma-D-Glu-L-Trp) with a specific activity of 45 Ci/mmol was obtained by high-temperature solid-state catalytic isotope exchange. It was found that [3H]bestim binds with a high affinity to murine peritoneal macrophages (Kd 2.1 +/- 0.1 nM) and thymocytes (Kd 3.1 +/- 0.2 nM), as well as with plasma membranes isolated from these cells (Kd 18.6 +/- 0.2 and 16.7 +/- 0.3 nM, respectively). The specific binding of [3H]bestim to macrophages and thymocytes was inhibited by the unlabeled dipeptide thymogen (L-Glu-L-Trp) (Ki 0.9 +/- 0.1 and 1.1 +/- 0.1 nM, respectively). After treatment with trypsin, macrophages and thymocytes lost the ability to bind [3H]bestim. Bestim in the concentration range of 10(-10) to 10(-6) M reduced the adenylate cyclase activity in the membranes of murine macrophages and thymocytes.
Asunto(s)
Adenilil Ciclasas/metabolismo , Membrana Celular/metabolismo , Dipéptidos/farmacología , Factores Inmunológicos/farmacología , Timo/enzimología , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Humanos , Macrófagos Peritoneales , Ratones , Ratones Endogámicos BALB C , Unión Proteica/fisiología , Timo/citologíaRESUMEN
Tritium-labeled synthetic fragments of human adrenocorticotropic hormone (ACTH) [3H]ACTH (11-24) and [3H]ACTH (15-18) with a specific activity of 22 and 26 Ci/mmol, respectively, were obtained. It was found that [3H]ACTH (11-24) binds to membranes of the rat adrenal cortex with high affinity and high specificity (Kd 1.8 +/- 0.1 nM). Twenty nine fragments of ACTH (11-24) were synthesized, and their ability to inhibit the specific binding of [3H]ACTH (11-24) to adrenocortical membranes was investigated. The shortest active peptide was found to be an ACTH fragment (15-18) (KKRR) (Ki 2.3 +/- 0.2 nM), whose [3H] labeled derivative binds to rat adrenocortical membranes (Kd 2.1 +/- 0.1 nM) with a high affinity. The specific binding of [3H]ACTH-(15-18) was inhibited by 100% by unlabeled ACTH (11-24) (Ki 2.0 +/- 0.1 nM). ACTH (15-18) in the concentration range of 1-1000 nM did not affect the adenylate cyclase activity of adrenocortical membranes and, therefore, is an antagonist of the ACTH receptor.
Asunto(s)
Corteza Suprarrenal/metabolismo , Hormona Adrenocorticotrópica/farmacología , Membrana Celular/metabolismo , Oligopéptidos/farmacología , Receptores de Corticotropina/antagonistas & inhibidores , Adenilil Ciclasas/metabolismo , Corteza Suprarrenal/citología , Hormona Adrenocorticotrópica/síntesis química , Hormona Adrenocorticotrópica/química , Animales , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Humanos , Oligopéptidos/síntesis química , Oligopéptidos/química , Unión Proteica/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Corticotropina/metabolismoRESUMEN
The tritium-labeled selective agonist of the nonopioid beta-endorphin receptor the decapeptide immunorphin ([3H]SLTCLVKGFY) with a specific activity of 24 Ci/mmol was prepared. It was shown that [3H]immunorphin binds with a high affinity to the non-opioid beta-endorphin receptor of mouse peritoneal macrophages (Kd 2.4 +/- 0.1 nM). The specific binding of [3H]immunorphin to macrophages was inhibited by unlabeled beta-endorphin (Ki of the [3H]immunorphin-receptor complex 2.9 +/- 0.2 nM) and was not inhibited by unlabeled naloxone, alpha-endorphin, gamma-endorphin, and [Met5]enkephalin (Ki > 10 microM). Thirty fragments of beta-endorphin were synthesized, and their ability to inhibit the specific binding of [3H]immunorphin to macrophages was studied. It was found that the shortest peptide having practically the same inhibitory activity as beta-endorphin is its fragment 12-19 (Ki 3.1 +/- 0.3 nM).
Asunto(s)
Macrófagos Peritoneales/metabolismo , Neurotransmisores/farmacología , Oligopéptidos/farmacología , Receptores Opioides/agonistas , betaendorfina/farmacología , Animales , Humanos , Ratones , Ratones Endogámicos BALB C , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Neurotransmisores/síntesis química , Oligopéptidos/síntesis química , Unión Proteica , Receptores Opioides/metabolismo , betaendorfina/síntesis químicaRESUMEN
We found that the tritium-labeled synthetic ACTH-like octapeptide leucocorticotropin corresponding to the 81-88 sequence of the precursor of human interleukin-1alpha ([3H]GKVLKKRR) is bound by the ACTH receptor of rat adrenal cortex with a high affinity and specificity (Kd 2.2 +/- 0.1 nM). This peptide was shown to exert no effect on the adenylate cyclase activity of the membranes of rat adrenal cortex in the concentration range from 1 to 1000 nM. Leucocorticotropin administration three times at doses of 10-20 microg/animal did not change the level of hydroxycorticosteroids (11-HOCS) in the rat adrenal glands in the absence of temperature action. At the same time, the peptide abolishes (at a dose of 20 microg/animal, three times) or significantly decreases (at a dose of 10 microg/animal, three times) the dramatic increase in the 11-HOCS content in the adrenal glands occurring in the case of cold or heat shock. Thus, leucocorticotropin normalizes the 11-HOCS level in the rat adrenal cortex during stress. The stress-protective effect of the peptide is mediated through the ACTH receptor.
Asunto(s)
Corticoesteroides/metabolismo , Corteza Suprarrenal/efectos de los fármacos , Interleucina-1alfa/farmacología , Fragmentos de Péptidos/farmacología , Sustancias Protectoras/farmacología , Receptores de Corticotropina/agonistas , Estrés Fisiológico/prevención & control , Administración Intranasal , Corteza Suprarrenal/química , Corteza Suprarrenal/metabolismo , Corticoesteroides/análisis , Hormona Adrenocorticotrópica/química , Secuencia de Aminoácidos , Animales , Humanos , Interleucina-1alfa/química , Interleucina-1alfa/metabolismo , Masculino , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/metabolismo , Sustancias Protectoras/química , Sustancias Protectoras/metabolismo , Ratas , Ratas Endogámicas , Receptores de Corticotropina/metabolismoRESUMEN
The synthetic peptide SLTCLVKGFY, corresponding to the 364-373 amino acid sequence of the human IgG heavy chain (Immunorphin), was found to compete with [125I] beta-endorphin for binding by high-affinity receptors on T lymphocytes isolated from the blood of healthy donors (Ki 0.6 nM). The fragments 3-10, 4-10, 5-10, and 6-10 of Immunorphin also inhibited the binding (Ki 2.2, 3.4, 8.0, and 15 nM, respectively). Specificity of these receptors was studied: they turned out to be insensitive to naloxone and, therefore, are not opioid. The Kd values of the specific binding of 125I-labeled Immunorphin and its 6-10 fragment to the receptor were found to be 7.4 and 36.3 nM, respectively.
Asunto(s)
Inmunoglobulina G/metabolismo , Cadenas Pesadas de Inmunoglobulina/metabolismo , Oligopéptidos/metabolismo , Fragmentos de Péptidos/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T/metabolismo , Unión Competitiva , Humanos , Regiones Constantes de Inmunoglobulina , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Pesadas de Inmunoglobulina/inmunología , Cadenas gamma de Inmunoglobulina , Oligopéptidos/genética , Oligopéptidos/inmunología , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/inmunología , betaendorfina/metabolismoRESUMEN
The antiproliferative and immunosuppressive in vitro effects of immunocortin, a synthetic adrenocorticotropin-like (ACTH-like) decapeptide H-Val-Lys-Lys-Pro-Gly-Ser-Ser-Val-Lys-Val-OH, whose sequence corresponds to segment 11-20 of the variable part of the human IgG1 heavy chain, were studied. At concentrations of 10(-11)-10(-7) M, immunocortin was found to inhibit the growth of the human MT-4 T-lymphoblastoid cell line, to suppress the blast transformation of thymocytes, and to decrease the spontaneous mobility of peritoneal macrophages and their bactericidal action toward the virulent strain Salmonella typhimurium 415. By using a 125I-labeled "addressing" fragment of ACTH ¿[125I]ACTH-(13-24)¿, we showed that MT-4 cells express specific receptors for ACTH (Kd 97 pM). Immunocortin and human ACTH (but not the heavy chain of IgG1) competitively inhibited the binding of [125I]ACTH-(13-24) to these receptors with Ki1 of 0.38 and Ki2 of 0.34 nM, respectively. Specific receptors for ACTH (Kd 5.8 nM) on mouse thymocytes were detected and characterized. The unlabeled immunocortin was shown to complete with labeled ACTH-(13-24) for binding to these receptors (Ki = 1.8 nM) and this binding of immunocortin to receptors on thymocytes activates adenylate cyclase from these cells and increases the intracellular concentration of cAMP.
Asunto(s)
Hormona Adrenocorticotrópica/genética , Inmunoglobulina G/genética , Inmunoglobulina G/metabolismo , Oligopéptidos , Hormona Adrenocorticotrópica/metabolismo , Animales , Humanos , Activación de Macrófagos , Macrófagos/metabolismo , Ratones , Oligopéptidos/síntesis química , Oligopéptidos/química , Oligopéptidos/genética , Oligopéptidos/metabolismo , Receptores de Corticotropina/metabolismo , Salmonella typhimuriumRESUMEN
A specific interaction of L-glutamic acid with promyelocytic leukemia HL-60 cells completely differentiated by all-E-retinoic acid (Kd = 0.5 microM) and by plasma membrane fraction from the same cells (Kd = 1 microM) was detected through radioligand analysis and characterized. Quisqualate, a nonlabeled structural analogue of glutamic acid, was found to inhibit competitively the specific binding of L-[3H]glutamic acid to the membranes (Ki = 0.24 microM). The stereospecificity of the binding was demonstrated. These data suggest that specific glutamate receptors appear on the surface of HL-60 cells during their differentiation.
Asunto(s)
Receptores de Glutamato/biosíntesis , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Fraccionamiento Celular , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Ácido Glutámico/metabolismo , Células HL-60 , Humanos , Ensayo de Unión Radioligante , Receptores de Glutamato/metabolismo , Tretinoina/farmacologíaRESUMEN
The effects of L-glutamic acid on the differentiation of HL-60 and K-562 cell lines and on the expression level of mRNAs encoding IL-1 beta, IL-6, and TNF alpha were studied. It was shown that TNF alpha actively induces the differentiation of these cell lines, whereas L-glutamic acid enhances its effect. Our results indicated that L-glutamic acid modulates the physiological state of the myeloid cell line in blood, in particular, by affecting both the reception and expression of cytokines functionally important for these cells.
Asunto(s)
Células de la Médula Ósea/efectos de los fármacos , Ácido Glutámico/farmacología , Células de la Médula Ósea/metabolismo , Diferenciación Celular/efectos de los fármacos , Células HL-60 , Humanos , Interleucina-1/genética , Interleucina-6/genética , Células K562 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
The effect of immunocortin, an ACTH-like decapeptide VKKPGSSVKV corresponding to the 11-20 sequence of the variable part of the human IgG1 heavy chain on the content of 11-hydroxycorticosteroids (CS) in rat adrenal glands and blood serum in vivo was studied. An intramuscular injection of immunocortin at a dose of 10 microg/kg was found in an hour to induce a twofold decrease in CS content in the adrenal glands and a 1.8-fold increase in the blood serum CS content. At the same time, an immunocortin dose of 100 microg/kg exerted practically no effect on the CS content and its dose of 1000 microg/kg increased the CS content both in adrenal glands and in blood serum by 1.6 and 2.2 times, respectively. Four hours after the injection of any of the three doses of immunocortin, the CS content in adrenal glands did not differ from the control value, and after 24 h the content decreased threefold. Immunocortin was shown to be bound by the ACTH receptors in the membranes of the rat adrenal cortex with a high affinity and specificity (inhibiting the specific binding of 125I-labeled ACTH-(11-24) peptide with Ki of 1.2 nM).
Asunto(s)
11-Hidroxicorticoesteroides/metabolismo , Corteza Suprarrenal/metabolismo , Hormona Adrenocorticotrópica/química , Inmunoglobulina G/química , Inmunoglobulina G/farmacología , Región Variable de Inmunoglobulina/química , Fragmentos de Péptidos/farmacología , 11-Hidroxicorticoesteroides/sangre , Corteza Suprarrenal/citología , Corteza Suprarrenal/efectos de los fármacos , Secuencia de Aminoácidos , Animales , Cosintropina/administración & dosificación , Cosintropina/farmacología , Inmunoglobulina G/administración & dosificación , Técnicas In Vitro , Radioisótopos de Yodo , Masculino , Datos de Secuencia Molecular , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/química , Ratas , Ratas Wistar , Receptores de Corticotropina/metabolismoRESUMEN
Six-membered peptide fragment TGENHR (HLDF-6) was identified in the HL-60 cell culture of human promyelocyte leukemia treated with retinoic acid when studying the differentiation factor HLDF of this cell line. HLDF-6 retains the ability of the full-size factor to induce the differentiation and arrest the proliferation of the starting HL-60 cells. It was shown that the synthetic peptide HLDF-6 has no specific receptors on the surface of the HL-60 cells but can affect the binding of interleukin IL-1 beta, a cytokine involved in proliferation, to the cell surface. It was found on a model of transplantable NSO myeloma that HLDF-6 has an antitumor activity.
Asunto(s)
Antineoplásicos/química , Proteínas de Neoplasias/química , Fragmentos de Péptidos/química , Animales , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Diferenciación Celular , División Celular/efectos de los fármacos , Células HL-60 , Humanos , Interferón-alfa/metabolismo , Interleucina-1/metabolismo , Masculino , Fluidez de la Membrana/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/farmacología , Unión Proteica , Proteínas Recombinantes/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Biologically active fragment 131-138 of human interferon alpha 2 carrying blast-transforming activity of the protein was attached to the N-terminus of the de novo protein albebetin with predetermined tertiary structure by means of genetic engineering. The chimeric protein was expressed in a wheat germ cell-free translation system and tested for compactness, stability and biological activity. According to the tests used albebetin with interferon fragment has a compact and relatively stable structure. It binds murine thymocyte receptor with high affinity and activates efficiently thymocyte blast transformation at a concentration of 10(-11) M.
Asunto(s)
Interferón-alfa/química , Fragmentos de Péptidos/química , Secuencia de Aminoácidos , Secuencia de Bases , Datos de Secuencia Molecular , Oligonucleótidos , Estructura Terciaria de Proteína , Proteínas/química , Proteínas Recombinantes de Fusión/química , Timo/química , Timo/citologíaRESUMEN
We studied the effect of synthetic peptides PEDF-6 and HLDF-6 on preimplantation development of mouse embryos in vitro. PEDF-6 peptide corresponds to fragment 351-356 and of pigment epithelium-derived differentiation factor (PEDF), while HLDF-6 peptide corresponds to fragment 84-89 of differentiation factor HLDF isolated from HL-60 cell line. Despite high homology, these peptides had different effects on the early development. PEDF-6 had no effect on the cleavage of 2-4-cell embryos but decelerated blastocyst formation from such embryos and disturbed their structure. In the presence of HLDF-6 the blastomeres divided more actively as compared to the control and a higher number of embryos developed to the blastocyst stage. The effects of both peptides were stage-specific: the affect the embryos at early cleavage stages and, apparently, determine their further development at that moment although do not directly affect formation of the blastocysts.