A novel cyclic undecapeptide, Wy-40,770, with prolonged growth hormone release inhibiting activity

Sarantakis, Dimitri; Teichman, J.; Lien, Eric L.; Fenichel, Richard L.

doi:10.1016/0006-291x(76)90712-9

Cited by 82 publications

(32 citation statements)

References 12 publications

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“…As a result the coupling with the relatively unreactive high molecular weight secondary amine 8 had to proceed despite low concentration of the acyl component. A variety of potent coupling reagents such as CIP, [51] DIC, [52] HATU, [53] PyBOP, [43] PyBroP [54] and TFFH [55] was evaluated by HPLC analysis of the crude material furnished upon acidmediated release, however, with little success. Thiazole orange dissolves at acidic pH and we therefore evaluated coupling reactions in the presence of acidic additives such as pyridinium para-toluenesulfonate (PPTS), pyridinium hydrobromide and tetrazole.…”

Section: Divergent Solid-phase Synthesismentioning

confidence: 99%

Divergent and Linear Solid‐Phase Synthesis of PNA Containing Thiazole Orange as Artificial Base

et al. 2005

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Fluorescent nucleobase surrogates provide nucleic acids with interesting properties. We have recently introduced thiazole orange as base surrogate into PNA and found that the so-called FIT (Forced Intercalation of Thiazole orange) PNA probes signal hybridization by enhancements of fluorescence. Common approaches of modifying nucleobases or introducing nucleobase surrogates draw upon the usage of monomer building blocks that have been synthesized in solution phase. The need to prefabricate a base-modified building block can hold up progress if several base modifications or base surrogates are to be evaluated. Herein, a method for divergent solid-phase synthesis is presented that serves the

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Section: Divergent Solid-phase Synthesismentioning

confidence: 99%

Divergent and Linear Solid‐Phase Synthesis of PNA Containing Thiazole Orange as Artificial Base

et al. 2005

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“…In route A, Rink amide aminomethyl (AM) 41 resin was employed, and the Fmoc-protected amino acids (2.5 eq) were sequentially coupled using the 1,3-diisopropylcarbodiimide (DIPCDI, 2.5 eq)-HOBt (N-hydroxybenzotriazole, 2.5 eq) method (2 h) 42 after the removal of each Fmoc group with 20% piperidine/ DMF (DMF: dimethylformamide; 20 min). The resulting peptide resin was cleaved with TFA-mcresol-thioanisole-H 2 O (TFA: triflouroacetic acid; 92.5:2.5:2.5:2.5) 43,44 for 90 min.…”

Section: Novel and Efficient Synthesis Of Difficult Sequence-containimentioning

confidence: 99%

ON intramolecular acyl migration reaction in the development of prodrugs and the synthesis of difficult sequence‐containing bioactive peptides

et al. 2004

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N-Ointramolecular acyl migration in Ser- or Thr-containing peptides is a well-known side reaction in peptide chemistry. It results in the mutual conversion of ester and amide bonds. Our medicinal chemistry study focused on the fact that the O-acyl product can be readily converted to the original N-acyl form under neutral or slightly basic conditions in an aqueous buffer and the liberated ionized amino group enhances the water solubility of O-acyl products. Because of this, we have developed a novel class of "O-N intramolecular acyl migration"-type water-soluble prodrugs of HIV-1 protease inhibitors. These prodrugs released the parent drugs via a simple chemical mechanism with no side reaction. In this study, we applied this strategy to important cancer chemotherapeutic agents, paclitaxel and its derivatives, to develop water-soluble taxoid prodrugs, and found that these prodrugs, 2'-O-isoform of taxoids, showed promising results with higher water solubility and proper kinetics in their parent drug formation by a simple pH-dependent chemical mechanism with O-N intramolecular acyl migration. These results suggest that this strategy would be useful in toxicology and medical economics. After the successful application of O-N intramolecular acyl migration in medicinal chemistry, this concept was recently used in peptide chemistry for the synthesis of "difficult sequence-containing peptides." The strategy was based on hydrophilic O-acyl isopeptide synthesis followed by the O-N intramolecular acyl migration reaction, leading to the desired peptide. In a model study with small, difficult sequence-containing peptides, synthesized "O-acyl isopeptides" not only improved the solubility in various media and efficiently performed the high performance liquid chromatography purification, but also altered the nature of the difficult sequence during SPPS, resulting in the efficient synthesis of O-acyl isopeptides with no complications. The subsequent O-N intramolecular acyl migration of purified O-acyl isopeptides afforded the desired peptides as precipitates with high yield and purity. Further study of the synthesis of a larger difficult sequence-containing peptide, Alzheimer's disease-related peptide (A beta 1-42), surprisingly showed that only one insertion of the O-acyl group drastically improved the unfavorable nature of the difficult sequence in A beta 1-42, and achieved efficient synthesis of 26-O-acyl isoA beta 1-42 and subsequent complete conversion to A beta 1-42 via the O-N intramolecular acyl migration reaction of 26-O-acyl isoA beta 1-42. This suggests that our new method based on O-N intramolecular acyl migration is an important method for the synthesis of difficult sequence-containing bioactive peptides.

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“…The Fmoc group was removed by reacting the resin three times with a mixture of piperidine and DMF (1:1, v/v: 1, 9 and 1 min) followed by washing with DMF (3 Â 1 min), MeOH (2 Â 1 min) and DMF (4 Â 1 min). In the course of coupling of the next amino acid residue, 200% molar excess of Fmoc-amino acid and of HOBt 19 and DIC 20 were dissolved in 2.0-2.5 ml DMF. The solution was allowed to stand for 5 min, added to the resin and the slurry was shaken for 90 min.…”

Section: Synthesis Of Peptidesmentioning

confidence: 99%

Chemotactic activity of oligopeptides containing an EWS motif on Tetrahymena pyriformis: the effect of amidation of the C‐terminal residue

Kőhidai

Bősze

Soós

et al. 2002

Cell Biochemistry & Function

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Chemotactic properties of 3-7-mer peptides containing an EWS motive and their peptide amides synthesized and characterized by us were investigated in Tetrahymena pyriformis GL model. Analysis of the peptide acids shows that SEWS possesses exceptionally strong (660%+/-21; 430%+/-18) chemoattractant ability at 10(-12) and 10(-11) m respectively. The shorter peptide (EWS) possesses chemorepellent activity, while longer peptides display neutral (WSEWS) or moderate chemoattractant (EWSEWS and GEWSEWS) chemotactic ability. Amidation of the C-terminus can significantly modify the character of peptides: it points to the conclusion that a free alpha-COOH group at this position is required for the high efficiency of SEWS, while in the shorter (EWS) and longer peptides (WSEWS and EWSEWS) amidation can result in chemoattractant ligands. Evaluation of the structure-function relationship of these compounds establishes the significance of Glu (E) with its high surface-exposed area and negatively-charged side chain. The high discriminative ability and good chemotactic responsiveness of Tetrahymena support the theory that a chemotactic signalling mechanism working in higher levels of phylogeny is a well conserved and inducible one even in protozoa.

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A novel cyclic undecapeptide, Wy-40,770, with prolonged growth hormone release inhibiting activity

Cited by 82 publications

References 12 publications

Divergent and Linear Solid‐Phase Synthesis of PNA Containing Thiazole Orange as Artificial Base

Divergent and Linear Solid‐Phase Synthesis of PNA Containing Thiazole Orange as Artificial Base

ON intramolecular acyl migration reaction in the development of prodrugs and the synthesis of difficult sequence‐containing bioactive peptides

Chemotactic activity of oligopeptides containing an EWS motif on Tetrahymena pyriformis: the effect of amidation of the C‐terminal residue

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