1,721,113 research outputs found
PEPTIDE SCIENCE IN THE YEARS TO COME
No full textBioactive peptides, exhibit a remarkable range of biological properties, but their utilization for clinical purposes such as diagnostic or therapeutics has some serious drawbacks and disadvantages. The main obstacles are their susceptibility to attack by proteolytic enzymes, their poor bioavailability, and for some of them, the difficulty of exerting centra I nervous effects after peripheral administration. Many efforts will be made in the near future by peptide chemists, in diverse areas of therapeutics such as the search of new drugs, active on the nervous system and capable of producing those typical, analgesic effects which led to the clinical use of opiates, but devoid of undesirable properties. Another object deals with anti-microbial peptides. Under the selective pressure exerted by the use and misuse of conventional antibiotics, bacteria are rapidly gaining resistance to these drugs and the search for novel antibacterial agents is in high demand
Bioactive peptide-peptoid hybrids
No full textThe synthesis and characterization are reported of peptide-peptoid hybrids of [Thr(6)]-bradykinin and some opioid and antimicrobial peptides. The tyrosine, phenylalanine, valine and arginine residues were partially or total replaced by N-alkyl- glycine residues. The sub-monomer method was used to build N-substituted glycines during peptide elongation. Preliminary pharmacological experiments showed that replacement of a single amino acid residue may result in peptide-peptoid hybrids that retain selective and biomimetic agonistic activity. However multiple substitutions generally induce a more or less marked worsening of the peptide pharmacological properties
Conjugation of photosensitisers to antimicrobial peptides increases the efficiency of photodynamic therapy in cancer cells
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On the Role of Basic Residues of Head-to-Tail Cyclic Bradykinin Analogues on Rat Duodenum Relaxation
No full textConformational investigations on glycosylated threonine-oligopeptides of increasing chain length
No full textStepwise solution syntheses are described of the homo-oligomers Z-(Thr)(n)-NHCH3 (n=1-4, I1-4), Z- ([Gal(Ac)(4) beta]Thr](n)-NHCH3 (n=1-5, II1-5] and Z[(Gal beta)Thr]n-NHCH3 (n=1-5, III1-5). Members of the III1-5 series were obtained by de-acetylation of the corresponding oligomers of the II1-5 series. The conformational preferences of the terminally protected homo-peptides of the three series were investigated by FT-IR absorption spectroscopy both in the solid state and in CDCl3 solution, at various concentrations. Proton NMR measurements in CDCl3 and in DMSO-d(6) were also carried out and the effect of temperature variation on the chemical shifts of amide protons was determined in DMSO-d(6) (range 298-335 K) and in CDCl3 (range 298- 320 K). CD spectra were recorded in water and in TFE. Solubility problems prevented measurements in CDCl3 solution for Z(Thr)(4)-NHCH3 and for the entire III1-5 series. The existence of unordered structures in the carbohydrate-free oligomers and of more or less extended, organized structures in the glycosylated derivatives is indicated by the NMR and IR measurements. The sugar moieties apparently show a structure-inducing effect on the peptide chain. (C) 1998 European Peptide Society and John Wiley Br Sons, Ltd
Synthesis of Glycosylated Tuftsins and Tuftsin-containing IGg Fragment Undecapeptide
No full textSyntheses are described of two new tuftsin derivatives containing a 2-acetamido-2-deoxy-D-galactopyranosyl unit alpha- or beta-glycosidically linked to the threonine's hydroxy side chain function and of the glycosylated undecapeptide corresponding to the tuftsin region of the heavy chain of IgG (amino acid sequence 289-299). The glycosylated tuftsins were synthesized by the solution procedure. Fmoc-[Gal NAc(Ac)3-alpha]Thr-OH and Fmoc-[GalNAc(Ac)3-beta]Thr-OH were allowed to react with H-Lys(Z)-Pro-Arg(NO2)-OBzl by the mixed anhydride procedure and the resulting glycosylated tetrapeptides were fully deblocked by catalytic hydrogenation followed by treatment with potassium cyanide, purified by ion exchange chromatography and characterized by analytical HPLC, elemental and amino acid analyses, optical rotation, and proton NMR spectroscopy. Synthesis of the glycosylated undecapeptide was achieved by the continuous flow solid phase procedure on 4-hydroxymethylphenoxyacetyl-norleucyl derivatized Kieselguhr-supported resin. Fmoc-amino acid symmetrical anhydrides or pentafluorophenyl esters, in the presence of N-hydroxybenzotriazole, were used as the acylating agents. To mimic the native sequence of the tuftsin region at the Fc-domain of immunoglobulin G a 2-acetamido-2-deoxy-beta-D-glucopyranosyl unit was N-glycosidically linked to the amide side chain of Asn 297. The glycosylated asparagine residue was introduced as N2-fluorenylmethyloxycarbonyl-N4-(2-acetamido-3,4, 6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-asparagine pentafluorophenyl ester. After cleavage from the resin the glycopeptide was deprotected, purified by ion exchange chromatography, and characterized by analytical HPLC, amino acid analysis, high voltage electrophoresis, and proton NMR. The conformational features of the glyco-undecapeptide were determined by circular dichroism measurements both in water and in 98% trifluoroethanol. Results of biological assays will be published elsewhere
Solution Synthesis of the Glyco-hexapeptide Sequence of the Human Oncofetal Fibronectin Defined By Monoclonal-antibody Fdc-6
No full textThe glyco-hexapeptide sequence H-Val-(GalNAc-alpha)Thr-His-Pro-Gly-Tyr-OH, was synthesized in solution by the segment condensation procedure and the stepwise procedure. A peracetylated, O-galactosaminyl threonine derivative was used for incorporating the glycosylated amino acid residue into the peptide chain. A consistent racemization occurred during the acylation of H-His-Pro-Gly-Tyr(Bzl)-OBzl with Z-Val-[GalNAc(Ac)3-alpha]Thr-OH by the BOP-HOBt procedure and the D-allothreonine containing glyco-hexapeptide was isolated in about 20% yield. Stepwise elongation of the C-terminal tetrapeptide with Fmoc-[GalNAc(Ac)3-alpha]Thr-OH and Z-Val-OH, in the presence of the same coupling reagents, yielded the L-threonine containing diastereoisomer without detectable racemization. A side product, the N(im)-ethoxy-carbonylated hexapeptide derivative, formed during the EEDQ-mediated condensation of Fmoc-[GalNAc(Ac)3-alpha]Thr-OH with the C-terminal tetrapeptide, was isolated and characterized. Preliminary studies showed that the synthetic glycohexapeptide is a good competitive inhibitor of the binding of the FDC-6 monoclonal antibody to the oncofetal fibronectin, supporting the idea that it should represent the minimum essential structure required for the FDC-6 activity
Cyclic Analogs of Thr(6)-bradykinin, N-epsilon-Lys-bradykinin and Endo-Lys(8a)-vespulakinin-1
No full textSyntheses are described of the endo-Lys(8a)-vespulakinin 1 and of cyclo-Thr(6)- and cyclo-N-epsilon-Lys-bradykinin. The linear peptides covering the entire sequences of endo-Lys(8a)-VSK-1 and Thr(6)-BK, and the decapeptide containing all residues constituting Lys-BK, with a Arg-Lys peptide bond involving the epsilon-amino function of lysine, were prepared by the solid-phase procedure based on Fmoc chemistry. Cyclization was carried out by the diphenylphosphorazide method. The amino-terminal octapeptide sequence of vespulakinin 1, Fmoc-Thr(tBu)-Ala-Thr(tBu)-Thr(tBu)-Arg(Pmc)-Arg(Pmc)-Arg(Pmc)-Gly-OH, and its N-alpha-Boc-[(Gal beta)Thr(3), (Gal beta)Thr(4)]-analogue, were used to prepare N-alpha-(1-8 VSK 1)-cyclo-N-epsilon-kallidin and N-alpha-[(Gal beta)Thr(3), (Gal beta)Thr(4), 1-8 VSK 1]-cyclo-N-epsilon-kallidin. Peptides and glycopeptides were characterized by amino-acid analysis, optical rotation, analytical HPLC and FAB-MS. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that the cyclic, or partially cyclic, analogues were significatively less potent than the linear ones. (C) Munksgaard 1995
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