1.
An activated triple bond linker enables 'click' attachment of peptides to oligonucleotides on solid support.
Source
Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 83 Huddinge, Sweden. malgorzata.wenska@ki.se
Abstract
A general procedure, based on a new activated alkyne linker, for the preparation of peptide-oligonucleotide conjugates (POCs) on solid support has been developed. With this linker, conjugation is effective at room temperature (RT) in millimolar concentration and submicromolar amounts. This is made possible since the use of a readily attachable activated triple bond linker enhances the Cu(I) catalyzed 1,3-dipolar cycloaddition ('click' reaction). The preferred scheme for conjugate preparation involves sequential conjugation to oligonucleotides on solid support of (i) an H-phosphonate-based aminolinker; (ii) the triple bond donor p-(N-propynoylamino)toluic acid (PATA); and (iii) azido-functionalizedpeptides. The method gives conversion of oligonucleotide to the POC on solid support, and only involves a single purification step after complete assembly. The synthesis is flexible and can be carried out without the need for specific automated synthesizers since it has been designed to utilize commercially available oligonucleotide and peptidederivatives on solid support or in solution. Methodology for the ready conversion of peptides into 'clickable' azidopeptides with the possibility of selecting either N-terminus or C-terminus connection also adds to the flexibility and usability of the method. Examples of synthesis of POCs include conjugates of oligonucleotides with peptides known to be membrane penetrating and nuclear localization signals.
Material binding peptides for nanotechnology.
Source
Luminous! Center of Excellence for Semiconductor Lighting and Displays, School of Electrical and Electronic Engineering, Microelectronics Division, School of Physical and Mathematical Sciences, Physics and Applied Physics Division, Nanyang Technological University, 639798 Singapore. uosseker@ntu.edu.sg or
Abstract
Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material bindingpeptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selectedpeptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.
- PMID:
- 21307821
- [PubMed - indexed for MEDLINE]
9-Fluorenylmethoxycarbonyl-based solid-phase synthesis of peptide α-thioesters.
Source
Humboldt-Universität zu Berlin, Institut für Chemie, Germany.
Abstract
Peptide thioesters play a key role in convergent protein synthesis strategies such as native chemical ligation, traceless Staudinger ligation, and Ag(+) -mediated thioester ligation. The Boc-based solid-phase synthesis provides a very reliable access to peptide thioesters. However, the acid lability of many peptide modifications and the requirements of most parallel peptide synthesizers call for the milder Fmoc-based solid-phase synthesis. The Fmoc-based synthesis ofpeptide thioesters is more cumbersome and typically proceeds with lower yields than the synthesis of peptide acids andpeptide amides. The success of native chemical ligation and related technologies has sparked intensive research effort devoted to the development of new methods. The recent progress in this rapidly expanding field is reviewed.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
9-Fluorenylmethoxycarbonyl-Based Solid-Phase Synthesis of Peptide α-Thioesters.
Source
Humboldt-Universität zu Berlin, Institut für Chemie, Brook-Taylor-Strasse 2, 12489 Berlin (Germany), Fax: (+49) 30-2093-7266.
Abstract
Peptide thioesters play a key role in convergent protein synthesis strategies such as native chemical ligation, traceless Staudinger ligation, and Ag(+)-mediated thioester ligation. The Boc-based solid-phase synthesis provides a very reliable access to peptide thioesters. However, the acid lability of many peptide modifications and the requirements of most parallel peptide synthesizers call for the milder Fmoc-based solid-phase synthesis. The Fmoc-based synthesis ofpeptide thioesters is more cumbersome and typically proceeds with lower yields than the synthesis of peptide acids andpeptide amides. The success of native chemical ligation and related technologies has sparked intensive research effort devoted to the development of new methods. The recent progress in this rapidly expanding field is reviewed.
Probing the molecular mechanisms of quartz-binding peptides.
Source
Department of Materials Science and Engineering, University of Washington, Seattle, Washington, USA.
Abstract
Understanding the mechanisms of biomineralization and the realization of biology-inspired inorganic materials formation largely depends on our ability to manipulate peptide/solid interfacial interactions. Material interfaces and biointerfaces are critical sites for bioinorganic synthesis, surface diffusion, and molecular recognition. Recently adapted biocombinatorial techniques permit the isolation of peptides recognizing inorganic solids that are used as molecular building blocks, for example, as synthesizers, linkers, and assemblers. Despite their ubiquitous utility in nanotechnology, biotechnology, and medicine, the fundamental mechanisms of molecular recognition of engineeredpeptides binding to inorganic surfaces remain largely unknown. To explore propensity rules connecting sequence, structure, and function that play key roles in peptide/solid interactions, we combine two different approaches: a statistical analysis that searches for highly enriched motifs among de novo designed peptides, and, atomistic simulations of three experimentally validated peptides. The two strong and one weak quartz-binding peptides were chosen for the simulations at the quartz (100) surface under aqueous conditions. Solution-based peptide structures were analyzed by circular dichroism measurements. Small and hydrophobic residues, such as Pro, play a key role at the interface by making close contact with the solid and hindering formation of intrapeptide hydrogen bonds. The high binding affinity of a peptide may be driven by a combination of favorable enthalpic and entropic effects, that is, a strong binder may possess a large number of possible binding configurations, many of which having relatively high binding energies. The results signify the role of the local molecular environment among the critical residues that participate in solid binding. The work herein describes molecular conformations inherent in material-specific peptides and provides fundamental insight into the atomistic understanding of peptide/solid interfaces.
Abrogation of TGF-beta1-induced fibroblast-myofibroblast differentiation by histone deacetylase inhibition.
Source
Biomedical Sciences Program, 1430 Tulane Ave. SL-9, Tulane Medical School, New Orleans, LA 70112, USA.
Abstract
Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no known effective pharmacological therapy. The fibroblastic foci of IPF contain activated myofibroblasts that are the major synthesizers of type I collagen. Transforming growth factor (TGF)-beta1 promotes differentiation of fibroblasts into myofibroblasts in vitro and in vivo. In the current study, we investigated the molecular link between TGF-beta1-mediated myofibroblast differentiation and histone deacetylase (HDAC) activity. Treatment of normal human lung fibroblasts (NHLFs) with the pan-HDAC inhibitor trichostatin A (TSA) inhibited TGF-beta1-mediated alpha-smooth muscle actin (alpha-SMA) and alpha1 type I collagen mRNA induction. TSA also blocked the TGF-beta1-driven contractile response in NHLFs. The inhibition of alpha-SMA expression by TSA was associated with reduced phosphorylation of Akt, and a pharmacological inhibitor of Akt blocked TGF-beta1-mediated alpha-SMA induction in a dose-dependent manner. HDAC4 knockdown was effective in inhibiting TGF-beta1-stimulated alpha-SMA expression as well as the phosphorylation of Akt. Moreover, the inhibitors of protein phosphatase 2A and 1 (PP2A and PP1) rescued the TGF-beta1-mediated alpha-SMA induction from the inhibitory effect of TSA. Together, these data demonstrate that the differentiation of NHLFs to myofibroblasts is HDAC4 dependent and requires phosphorylation of Akt.
Genetically designed Peptide-based molecular materials.
Source
Genetically Engineered Materials Science and Engineering, Department of Materials Science and Engineering, University of Washington, Seattle, Washington 98195.
Abstract
With recent developments of nanoscale engineering in the physical and chemical sciences and advances in molecular biology, molecular biomimetics is combining genetic tools and evolutionary approaches with synthetic nanoscale constructs to create a new hybrid methodology: genetically designed peptide-based molecular materials. Following the fundamental principles of genome-based design, molecular recognition, and self-assembly in nature, we can now use recombinant DNA technologies to design single or multifunctional peptides and peptide-based molecular constructs that can interact with solids and synthetic systems. These solid-binding peptides have made significant impact as inorganicsynthesizers, nanoparticle linkers, and molecular assemblers, or simply as molecular building blocks, in a wide range of fields from chemistry to materials science to medicine. As part of the programmatic theme, "Nanoscience: Challenges for the Future", the current developments, challenges, and future prospects of the field were presented during a symposium at the 237th ACS National Meeting held in March 2009. This Nano Focus article presents a synopsis of the work discussed there.
Molecular biomimetics: nanotechnology and bionanotechnology using genetically engineered peptides.
Source
Genetically Engineered Materials Science and Engineering Center, University of WashingtonSeattle, WA 98195, USA.
Abstract
Nature provides inspiration for designing materials and systems that derive their functions from highly organized structures. Biological hard tissues are hybrid materials having inorganics within a complex organic matrix, the molecular scaffold controlling the inorganic structures. Biocomposites incorporate both biomacromolecules such as proteins, lipids and polysaccharides, and inorganic materials, such as hydroxyapatite, silica, magnetite and calcite. The ordered organization of hierarchical structures in organisms begins via the molecular recognition of inorganics by proteins that control interactions and is followed by the highly efficient self-assembly across scales. Following the molecular biological principle, proteins could also be used in controlling materials formation in practical engineering via self-assembled, hybrid, functional materials structures. In molecular biomimetics, material-specific peptides could be the key in the molecular engineering of biology-inspired materials. With the recent developments of nanoscale engineering in physical sciences and the advances in molecular biology, we now combine genetic tools with synthetic nanoscale constructs to create a novel methodology. We first genetically select and/or design peptides with specific binding to functional solids, tailor their binding and assembly characteristics, develop bifunctional peptide/protein genetic constructs with both material binding and biological activity, and use these as molecular synthesizers, erectors and assemblers. Here, we give an overview of solid-binding peptides as novel molecular agents coupling bio- and nanotechnology.
Peptides grafted from solids for the control of interfacial properties.
Source
The Department of Chemical and Biomolecular Engineering and The Bio21 Molecular Health and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
Abstract
We have used solid-phase peptide synthesis to graft a peptide monolayer from a solid in order to modify the interfacial properties. We grafted a 15-residue peptide, EKEKEKEKEKEKEGG, containing a zwitterionic sequence of alternating lysine and glutamic acid residues from the surface of an aminosilanized silicon wafer by placing the silicon wafer within a commercial microwave peptide synthesizer. Such synthesizers are routinely used to make peptides on porous beads, but the peptides are subsequently cleaved and used independently of the solid support; our aim is to utilize the covalently bound peptide to control the surface properties without the need for cleavage and reattachment. We confirmed the presence of this peptide layer on the surface by X-ray photoelectron spectroscopy and ellipsometry. Atomic force microscopy was then used to study the forces between the peptide-modified surface and a borosilicate glass sphere as a function of the solution pH. The adsorbed peptide makes the silicon wafer pH responsive: at high pH the glass particle is repelled from the wafer, and at low pH it is attracted. Previous studies with synthetic polymers have shown that the "grafting from" method allows a much higher film density than "grafting to". We propose that the application of grafting from strategies to peptide layers may offer three additional benefits: (1) the film density can be controlled independently of the primary sequence of the peptide, (2) the sequence constraints for spontaneous adsorption are removed, and (3) the procedure is fast and efficient, which may lead to lower costs and the ability for high-throughput surface biofunctionalization. Moreover, peptide layers offer increased sequence diversity, control, and functionality compared to conventional polymer brushes.
Effect of molecular conformations on the adsorption behavior of gold-bindingpeptides.
Source
Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.
Abstract
Despite extensive recent reports on combinatorially selected inorganic-binding peptides and their bionanotechnological utility as synthesizers and molecular linkers, there is still only limited knowledge about the molecular mechanisms ofpeptide binding to solid surfaces. There is, therefore, much work that needs to be carried out in terms of both the fundamentals of solid-binding kinetics of peptides and the effects of peptide primary and secondary structures on their recognition and binding to solid materials. Here we discuss the effects of constraints imposed on FliTrx-selected gold-binding peptide molecular structures upon their quantitative gold-binding affinity. We first selected two novel gold-bindingpeptide (AuBP) sequences using a FliTrx random peptide display library. These were, then, synthesized in two different forms: cyclic (c), reproducing the original FliTrx gold-binding sequence as displayed on bacterial cells, and linear (l) dodecapeptide gold-binding sequences. All four gold-binding peptides were then analyzed for their adsorption behavior using surface plasmon resonance spectroscopy. The peptides exhibit a range of binding affinities to and adsorption kinetics on gold surfaces, with the equilibrium constant, Keq, varying from 2.5x10(6) to 13.5x10(6) M(-1). Both circular dichroism and molecular mechanics/energy minimization studies reveal that each of the four peptides has various degrees of random coil and polyproline type II molecular conformations in solution. We found that AuBP1 retained its molecular conformation in both the c- and l-forms, and this is reflected in having similar adsorption behavior. On the other hand, the c- and l-forms of AuBP2 have different molecular structures, leading to differences in their gold-binding affinities.
A personal journey of discovery: developing technology and changing biology.
Source
Institute for Systems Biology, Seattle, Washington 98103, USA. lhood@systemsbiology.org
Abstract
This autobiographical article describes my experiences in developing chemically based, biological technologies for deciphering biological information: DNA, RNA, proteins, interactions, and networks. The instruments developed include protein and DNA sequencers and synthesizers, as well as ink-jet technology for synthesizing DNA chips. Diverse new strategies for doing biology also arose from novel applications of these instruments. The functioning of these instruments can be integrated to generate powerful new approaches to cloning and characterizing genes from a small amount of protein sequence or to using gene sequences to synthesize peptide fragments so as to characterize various properties of the proteins. I also discuss the five paradigm changes in which I have participated: the development and integration of biological instrumentation; the human genome project; cross-disciplinary biology; systems biology; and predictive, personalized, preventive, and participatory (P4) medicine. Finally, I discuss the origins, the philosophy, some accomplishments, and the future trajectories of the Institute for Systems Biology.
- PMID:
- 20636073
- [PubMed - indexed for MEDLINE]
Synthesis of oligonucleotide derivatives using ChemMatrix supports.
Source
Institute for Research in Biomedicine, Barcelona Science Park, University of Barcelona, Spain.
Abstract
The synthesis of oligonucleotides on poly(ethylene glycol)-based (ChemMatrix) supports was studied. Results show that oligonucleotides can be indeed prepared in good yields using slightly modified synthesis cycles and automated DNAsynthesizers. The use of these supports for the synthesis of oligonucleotide-peptide conjugates and for the ligation of oligonucleotides using Cu(+)-catalyzed cycloadition reactions is reported. Moreover, these supports can be used for the preparation of oligonucleotides in anhydrous solvents, followed by hybridization of the complementary sequences in aqueous buffers.
Automated oligosaccharide synthesis.
Source
Laboratory for Organic Chemistry, Swiss Federal Institute of Technology (ETH) Zürich, HCI F 315, Wolfgang-Pauli-Str. 10, CH-8093 Zürich, Switzerland. seeberger@org.chem.ethz.ch
Abstract
Peptides and oligonucleotides are prepared by automated synthesizers that can be operated by non-specialists. Carbohydrates have been hard to assemble, but the increasing awareness of the biological importance of this class of complex repeating biopolymers has prompted efforts to accelerate their synthesis. This tutorial review defines the state of the art of automated solid phase oligosaccharide synthesis and identifies areas in need of further innovation. Application of the automated synthesis method to prepare a malaria vaccine candidate is briefly highlighted.
Adsorption behavior of linear and cyclic genetically engineered platinum binding peptides.
Source
Genetically Engineered Materials Science and Engineering Center, Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.
Abstract
Recently, phage and cell-surface display libraries have been adapted for genetically selecting short peptides for a variety of inorganic materials. Despite the enormous number of inorganic-binding peptides reported and their bionanotechnological utility as synthesizers and molecular linkers, there is still a limited understanding of molecular mechanisms of peptide recognition of and binding to solid materials. As part of our goal of genetically designing thesepeptides, understanding the binding kinetics and thermodynamics, and using the peptides as molecular erectors, in this report we discuss molecular structural constraints imposed upon the quantitative binding characteristics of peptides with an affinity for inorganics. Specifically, we use a high-affinity seven amino acid Pt-binding sequence, PTSTGQA, as we reported in earlier studies and build two constructs: one is a Cys-Cys constrained "loop" sequence (CPTSTGQAC) that mimics the domain used in the pIII tail sequence of the phage library construction, and the second is the linear form, a septapeptide, without the loop. Both sequences were analyzed for their adsorption behavior on Pt thin films by surface plasmon resonance (SPR) spectroscopy and for their conformational properties by circular dichroism (CD). We find that the cyclic peptide of the integral Pt-binding sequence possesses single or 1:1 Langmuir adsorption behavior and displays equilibrium and adsorption rate constants that are significantly larger than those obtained for the linear form. Conversely, the linear form exhibits biexponential Langmuir isotherm behavior with slower and weaker binding. Furthermore, the structure of the cyclic version was found to adopt a random coil molecular conformation, whereas the linear version adopts a polyproline type II conformation in equilibrium with the random coil. The 2,2,2-trifluoroethanol titration experiments indicate that TFE has a different effect on the secondary structures of the linear and cyclic versions of the Pt binding sequence. We conclude that the presence of the Cys-Cys restraint affects both the conformation and binding behavior of the integral Pt-binding septapeptide sequence and that the presence or absence of constraints could be used to tune the adsorption and structural features of inorganic binding peptide sequences.
Nitric oxide in cerebrospinal fluid and local inducible nitric oxide synthase after cauda equina compression in rats.
Source
Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata University, Niigata-shi, Niigata, Japan.
Abstract
We investigated the time course of changes in nitric oxide metabolite (NO2- plus NO3-: NOx) levels in the cerebrospinal fluid and the expression of local inducible nitric oxide synthase following cauda equina compression in rats. Cerebrospinal fluid NOx levels were significantly increased from 12 h to 3 days after compression, and decreased thereafter. Histologically, inducible nitric oxide synthase immunoreactivity was observed in macrophages that infiltrated the dura mater on days 1 and 3 after compression, but not in foamy macrophages in the parenchyma of the cauda equina observed afterwards. The pattern of NOx levels coincided with the appearance of inducible nitric oxide synthase labeled macrophages, indicating a critical role of these cells as the main synthesizers of NOx in the acute stage of cauda equina compression.
Synthetic histidine-rich peptides inhibit Candida species and other fungi in vitro: role of endocytosis and treatment implications.
Source
Department of Pathology, University of Maryland Baltimore, Baltimore, MD 21201, USA.
Abstract
A family of histidine-rich peptides, histatins, is secreted by the parotid gland in mammals and exhibits marked inhibitory activity against a number of Candida species. We were particularly interested in the mechanism by which histidine-richpeptides inhibit fungal growth, because our laboratory has synthesized a variety of such peptides for drug and nucleic acid delivery. In contrast to naturally occurring peptides that are linear, peptides made on synthesizers can be varied with respect to their degrees of branching. Using this technology, we explored whether histidine-lysine (HK) polymers of different complexities and degrees of branching affect the growth of several species of Candida. Polymers with higher degrees of branching were progressively more effective against Candida albicans, with the four-branched polymer, H2K4b, most effective. Furthermore, H2K4b accumulated efficiently in C. albicans, which may indicate its ability to transport other antifungal agents intracellularly. Although H2K4b had greater antifungal activity than histatin 5, their mechanisms were similar. Toxicity in C. albicans induced by histatin 5 or branched HK peptides was markedly reduced by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonate, an inhibitor of anion channels. We also determined that bafilomycin A1, an inhibitor of endosomal acidification, significantly decreased the antifungal activity of H2K4b. This suggests that the pH-buffering and subsequent endosomal-disrupting properties of histidine-rich peptides have a role in their antifungal activity. Moreover, the ability of the histidine component of these peptides to disrupt endosomes, which allows their escape from the lysosomal pathway, may explain why these peptides are both effective antifungal agents and nucleic acid delivery carriers.
RANKL in human periapical granuloma: possible involvement in periapical bone destruction.
Source
Periodontal Biology Laboratory, Dentistry Faculty, University of Chile, Santiago, Chile. rvernal@uchile.cl
Abstract
OBJECTIVES:
The cytokine receptor activator of nuclear factor kappaB-ligand (RANKL) has been involved in both the physiological and pathological regulation of osteoclast life span and bone metabolism. Periapical granuloma is a periradicular lesion characterized by periapical bone destruction. The aims of this study were to associate the RANKL mRNA levels to periapical granulomas using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to determine the specific cell involved in RANKL synthesis.
METHODS:
In eight periapical granuloma and eight periodontal ligament samples from periodontally healthy volunteers, RANKL mRNA was detected by real-time RT-PCR. Expression of RANKL on infiltrate leukocytes was further investigated by flow cytometry in six periapical granulomas.
RESULTS:
Receptor activator of nuclear factor kappaB-ligand mRNA levels were higher in periapical granulomas than in healthy periodontal ligament as its RANKL mRNA cycle threshold (Ct) and DeltaCt were significantly lower than that of controls (33.07 +/- 1.24 vs 36.96 +/- 1.69 and 11.58 +/- 3.02 vs 15.60 +/- 3.31, respectively). A 16.2-fold (2.0-131.6) higher RANKL gene expression was detected in the granulomas compared with the control tissues. We determined by flow cytometry that lymphocytes were the predominant leukocyte cells (53.31%), and monocytes and dendritic cells were the main RANKL synthesizers in granuloma lesions.
CONCLUSIONS:
These data indicate that monocytes synthesized RANKL in periapical granulomas and suggest that RANKL is involved in bone loss associated with periapical lesions.
Multi-line split DNA synthesis: a novel combinatorial method to make high quality peptide libraries.
Source
Tokyo Evolution Research Center, 1-1-45-504, Okubo, Shinjuku-ku, Tokyo 169-0072, Japan. tabuchii@mx16.freecom.ne.jp
Abstract
BACKGROUND:
We developed a method to make a various high quality random peptide libraries for evolutionary protein engineering based on a combinatorial DNA synthesis.
RESULTS:
A split synthesis in codon units was performed with mixtures of bases optimally designed by using a Genetic Algorithm program. It required only standard DNA synthetic reagents and standard DNA synthesizers in three lines. This multi-line split DNA synthesis (MLSDS) is simply realized by adding a mix-and-split process to normal DNA synthesis protocol. Superiority of MLSDS method over other methods was shown. We demonstrated the synthesis of oligonucleotide libraries with 1016 diversity, and the construction of a library with random sequence coding 120 amino acids containing few stop codons.
CONCLUSIONS:
Owing to the flexibility of the MLSDS method, it will be able to design various "rational" libraries by using bioinformatics databases.
A simple and effective method for producing nonrandom peptide libraries using cotton as a carrier in continuous flow peptide synthesizers.
Source
Department of Pharmaceutical Biosciences, Division of Pharmacology, Uppsala University, Box 591, Biomedicum, SE-751 24 Uppsala, Sweden.
Abstract
A method has been developed for generating nonrandom peptide libraries on cotton. Disks of cotton fabric were chemically modified to enable peptide synthesis. Incorporation of a 6-aminocaproic acid residue handle on the cellulose turned out to be advantageous. Disks were labeled with silver ink, stacked one on top of another in a continuous flowpeptide synthesizer column, and simultaneously subjected to automated synthesis procedures. Depending on the sequences to be synthesized, the automatic synthesis procedure was stopped, and the disks were removed from the column, sorted, and reapplied to subsequent synthesis steps. In this way, individual peptides could be easily prepared in milligram quantities on each of the cotton disks.
Solid-phase synthesis of oligourea peptidomimetics employing the Fmoc protection strategy.
Source
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, NL-3508 TB Utrecht, The Netherlands.
Abstract
A solid-phase-Fmoc-based-synthesis strategy is described for oligourea peptidomimetics as well as a convenient general synthesis approach for the preparation of the required building blocks 5a-j and 5k. These are suitable for use inpeptide or robot synthesizers, which is illustrated by the synthesis of oligourea peptidomimetics of part of Leu-enkephalin (10) and a neurotensin derivative (17).
- PMID:
- 11735525
- [PubMed - indexed for MEDLINE]
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