558 resultados para PRINS CYCLIZATION


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"November 1976."

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"March 1980."

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The behavior of [alpha]-monoglycerides.

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[1] Inledning. Valdemar Seier.--[2] Erik Menveds barndom.--[3]Kong Erik og de fredløse.--[4] Prins Otto af Danmark.

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"... quod, annuente summo numine, praeside Gisberto Joanne Rooijens, theol. doct. in ill. Amstel. Athen. theol. et hist. eccles. prog., ad publicam disceptationem proponit ..."

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Each work has individual title-page and pagination.

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"Tweede stukjen, zijnde een vervolg op de Inlichtingen omtrent het karakter van Prins Maurits van Nassau."

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Top Row: Clare L. Allen, Kathryn M. Antekeier, Debra Ayanian, Kristin E. Baker, Lynn A. Bluck, Linda A. Bochenek, Samatha Brennan, Julie A. Coburn, Anne E. Cooksey, Susan L. Cross, Kimberli S. Darvishian, Natalie, J. Dichtiar, Joanne M. Dork

Row 2: Mary K. Emerson, Marion A. Ferguson, Amy S. Fuhst, JAckie Vicari, Patti Geiman, Denise B. Sorenson, Lisa Maastricht, Karen L. Bloom, Natalie R. Geiss, Elizabeth A. Hamann, Liesl M. Hintermaier

Row 3: Cynthia M. Hubert, Mercedes Castro, Irene Hundt

Row 4: Kris A. Hurley, Katherine A. Jeffery, Kathy M. Jhung, Rebecca J. Kantor, Denise J. Kehrer, Colleen E. Kelly

Row 5: Judy A. Kettenstock, Rhonda L. Kinney, Kimberly Klarich, Kimberly J. Kdning, Dianne M. Kraft, Brenda M. LaChapelle

Row 6: Lavonne L. Lang, Laurie A. Langwerowski, Rebecca S. Leak, Sally Sample, Violet Barkauskas, Rhetaugh G. Dumas, Shake Ketefian, Janice B. Lindberg, Elisabeth Pennington, Sharon A. Libby, Bonnie M. McDonald, Patricia A. Mehall

Row 7: Kristen K. Miller, Kelley L. Ong, Alice I. Paik, Michelle L. Pardee, Edith H. Price, Anke Winkler-Prins, Lori L. reisig, Camille A. Rogell, Mindy A. Rosenberg, Richard E. Ross, Julie A. Sarotte, Laura A. Schippers, Rose M. Schliska, Marilyn H. Schwartz

Row 8: Heidi Simonelli, Victoria J. Sizemore, Diane L. Sorenson, Deborah R. Sproul, Katherine Stewart, Kim M. Strong, Barbara J. Sullivan, Pamela S. Taukert, Kristin A. Treash, Kimberly Vander Heuvel, Sherry Vanootighem, Annmarie Veraldi, Idella A. Wesselman

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Thesis (doctoral)--Universiteit van Amsterdam.

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Thesis (doctoral)--Universiteit van Amsterdam.

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Cyclic tetrapeptides are an intriguing class of natural products. To synthesize highly strained cyclic tetrapeptides; we developed a macrocyclization strategy that involves the inclusion of 2-hydroxy-6-nitrobenzyl (HnB) group at the N-terminus and in the middle of the sequence. The N-terminal auxiliary performs a ring closure/ring contraction role, and the backbone auxiliary promotes cis amide bonds to facilitate the otherwise difficult ring contraction. Following this route, the all-L cyclic tetrapeptide cyclo-[Tyr-Arg-Phe-Ala] was successfully prepared.

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Relatively few cyclic peptides have reached the pharmaceutical marketplace during the past decade, most produced through fermentation rather than made synthetically. Generally, this class of compounds is synthesized for research purposes on milligram scales by solid-phase methods, but if the potential of macrocyclic peptidomimetics is to be realized, low-cost larger scale solution-phase syntheses need to be devised and optimized to provide sufficient quantities for preclinical, clinical, and commercial uses. Here, we describe a cheap, medium-scale, solution-phase synthesis of the first reported highly potent, selective, and orally active antagonist of the human C5a receptor. This compound, Ac-Phe[Orn-Pro-D-Cha-Trp-Arg], known as 3D53, is a macrocyclic peptidomimetic of the human plasma protein C5a and displays excellent antiinflammatory activity in numerous animal models of human disease. In a convergent approach, two tripeptide fragments Ac-Phe-Orn-(Boc)-Pro-OH and H-D-Cha-Trp(For)-Arg-OEt were first prepared by high-yielding solution-phase couplings using a mixed anhydride method before coupling them to give a linear hexapeptide which, after deprotection, was obtained in 38% overall yield from the commercially available amino acids. Cyclization in solution using BOP reagent gave the antagonist in 33% yield (13% overall) after HPLC purification. Significant features of the synthesis were that the Arg side chain was left unprotected throughout, the component Boe-D-Cha-OH was obtained very efficiently via hydrogenation Of D-Phe with PtO2 in TFA/water, the tripeptides were coupled at the Pro-Cha junction to minimize racemization via the oxazolone pathway, and the entire synthesis was carried out without purification of any intermediates. The target cyclic product was purified (>97%) by reversed-phase HPLC. This convergent synthesis with minimal use of protecting groups allowed batches of 50100 g to be prepared efficiently in high yield using standard laboratory equipment. This type of procedure should be useful for making even larger quantities of this and other macrocyclic peptidomimetic drugs.

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Microcin J25 is a 21 amino acid bacterial peptide that has potent antibacterial activity against Gram-negative bacteria, resulting from its interaction with RNA polymerase. The peptide was previously proposed to have a head-to-tail cyclized peptide backbone and a tight globular structure (Blond, A., Peduzzi, J., Goulard, C., Chiuchiolo, M. J., Barthelemy, M., Prigent, Y., Salomon, R. A., Farias, R. N., Moreno, F. & Rebuffat, S. Eur. J. Biochem. 1999, 259, 747-755). It exhibits remarkable thermal stability for a peptide of its size lacking disulfide bonds and in part this was previously proposed to derive from its macrocyclic structure. We show here that in fact the peptide does not have a head-to-tail cyclic structure but rather a side chain to backbone cyclization between Glu8 and the N-terminus. This creates an embedded ring that is threaded by the C-terminal tail of the molecule, forming a noose-like feature. The three-dimensional structure deduced from NMR data suggests that slippage of the noose is prevented by two aromatic residues flanking the embedded ring. Unthreading does not occur even when the molecule is enzymatically digested with thermolysin. The new structural interpretation fully accounts for previously reported NMR and biophysical data and is consistent with the remarkable stability of this potent antimicrobial peptide.

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The presence of a diabetic cardiomyopathy, independent of hypertension and coronary artery disease, is still controversial. This systematic review seeks to evaluate the evidence for the existence of this condition, to clarify the possible mechanisms responsible, and to consider possible therapeutic implications. The existence of a diabetic cardiomyopathy is supported by epidemiological findings showing the association of diabetes with heart failure; clinical studies confirming the association of diabetes with left ventricular dysfunction independent of hypertension, coronary artery disease, and other heart disease; and experimental evidence of myocardial structural and functional changes. The most important mechanisms of diabetic cardiomyopathy are metabolic disturbances (depletion of glucose transporter 4, increased free fatty acids, carnitine deficiency, changes in calcium homeostasis), myocardial fibrosis (association with increases in angiotensin II, IGF-I, and inflammatory cytokines), small vessel disease (microangiopathy, impaired coronary flow reserve, and endothelial dysfunction), cardiac autonomic neuropathy (denervation and alterations in myocardial catecholamine levels), and insulin resistance (hyperinsulinemia and reduced insulin sensitivity). This review presents evidence that diabetes is associated with a cardiomyopathy, independent of comorbid conditions, and that metabolic disturbances, myocardial fibrosis, small vessel disease, cardiac autonomic neuropathy, and insulin resistance may all contribute to the development of diabetic heart disease.