RESUMEN
The bone marrow myelopeptides Phe-Arg-Pro-Arg-Ile-Met-Thr-Pro (MP-4) and Val-Asp-Pro-Pro (MP-6) have been synthesised by a classical method and by a solid phase synthesis. The differentiating activity of MP-4 and MP-6 in human leukemia cells HL-60 and K-562 has been studied. Both peptides induce terminal differentiation of these cell lines but the mechanism of action of peptides MP-4 and MP-6 is distinguished.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Oligopéptidos/síntesis química , Oligopéptidos/farmacología , Células HL-60 , Humanos , Células K562 , Oligopéptidos/químicaRESUMEN
Two variants of the synthesis of tridecapeptide alloferon, the active principle of antiviral preparation allokine-alpha, were developed on the basis of fragment condensation in solution or on the Merrifield resin. The solid phase variant of the synthesis was shown to be more technological; it allows the preparation of the product at a higher total yield (40% vs. 17% for conventional synthesis in solution from the starting derivatives of the C-terminal dipeptide). The by-products formed during the synthesis of alloferon were identified.
Asunto(s)
Adyuvantes Inmunológicos/síntesis química , Antivirales/síntesis química , Péptidos/síntesis química , Cromatografía Líquida de Alta PresiónRESUMEN
The use of hydrogen peroxide for the formation of disulfide bridges was studied in 15 peptides of various lengths and structures. The oxidation of peptide thiols by hydrogen peroxide was shown to proceed under mild conditions without noticeable side reactions of Trp, Tyr, and Met residues. Yields of the corresponding cyclic disulfides were high and mostly exceeded those obtained with other oxidative agents, in particular, iodine. It was established that the use of hydrogen peroxide in organic medium also provided sufficiently high yields when large-scale syntheses of oxytocin and octreotide (up to 10 g) were carried out. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 2; see also http://www.maik.ru.
Asunto(s)
Disulfuros/química , Peróxido de Hidrógeno/química , Péptidos/química , Secuencia de Aminoácidos , Cromatografía Líquida de Alta Presión , Oxidación-ReducciónRESUMEN
The linear precursors of endothelin 1 and endothelin 3, natural vasoactive peptides, were obtained by using the Boc- and Fmoc-schemes of solid phase peptide synthesis. The methods of directed and spontaneous formation of two disulfide bonds in the molecules of these precursors were compared and shown to give comparable results. The conditions were found that provided the selective S-S-ring closure in the methionine-containing endothelin 1 by means of hydrogen peroxide without the undesired conversion of the Met residue into the corresponding sulfoxide.
Asunto(s)
Disulfuros/química , Endotelina-1/síntesis química , Endotelina-3/síntesis química , Peróxido de Hidrógeno/química , Secuencia de Aminoácidos , Endotelina-1/química , Endotelina-3/química , Datos de Secuencia MolecularRESUMEN
Removal of Acm-protecting group from thiol functional groups of Cys residues with simultaneous disulfide bridge formation by iodine in acetic acid was studied in the course of the synthesis of a peptide fragment corresponding to 593-603 sequence of HIV-2 gp41 glycoprotein. The excess iodine influence on the cyclization process was investigated. By-products of the oxidative disulfide formation were isolated, and their structures were elucidated by means of amino acid and elemental analyses, mass spectrometry, NMR, and UV-spectroscopy.
Asunto(s)
Disulfuros/química , Proteína gp41 de Envoltorio del VIH/química , VIH-2/química , Fragmentos de Péptidos/química , Acetilcisteína/análogos & derivados , Acetilcisteína/química , Secuencia de Aminoácidos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Datos de Secuencia Molecular , Espectrofotometría UltravioletaRESUMEN
A simple, rapid, and highly efficient method for intramolecular disulfide formation in tryptophan-containing peptides using hydrogen peroxide was elaborated. Solid phase synthesis of the peptide fragment corresponding to 601-617 sequence of transmembrane gp41 glycoprotein of HIV-1 was performed by Fmoc-technique. Coupling of Fmoc-Asn-OH by DCC-HOBt method was shown to be accompanied by a side reaction of dehydration of asparagine amide function with the formation of side product (22%) containing 3-cyanoalanine residue. This side reaction was not observed, when Fmoc-Asn-OH was coupled in the form of its p-nitrophenyl ester and with HOBt as a catalyst.
Asunto(s)
Disulfuros/química , Proteína gp41 de Envoltorio del VIH/inmunología , VIH-1/química , Peróxido de Hidrógeno/química , Epítopos Inmunodominantes/química , Fragmentos de Péptidos/síntesis química , Secuencia de Aminoácidos , Epítopos Inmunodominantes/inmunología , Datos de Secuencia MolecularRESUMEN
Ethylamide of cyclic disulfide of peptide HIV-2 antigen corresponding to 593-603 sequence of gp41 protein was synthesized by conventional methods of peptide chemistry in solution. The absence of racemization during fragment condensation was shown. Different methods of disulfide bond formation were compared.
Asunto(s)
Amidas/síntesis química , Proteína gp41 de Envoltorio del VIH/química , VIH-2/química , Fragmentos de Péptidos/química , Fragmentos de Péptidos/síntesis química , Péptidos Cíclicos/síntesis química , Secuencia de Aminoácidos , Datos de Secuencia MolecularRESUMEN
Bombesin, some of its fragments and analogues, being injected intracerebroventricularly, induce rapid decline in body temperature. The active fragment of bombesin--C-terminal nonapeptide--induced a 25% depression of oxygen consumption in cold-exposed rabbits, no changes in the shivering thermogenesis, and a 3.5--5.0-fold increase of ear blood vessels section area accompanied by a gain in linear velocity of blood flow. The peripheral blood flow seems to be the main effector of the bombesin-induced hypothermia.