Synthesis of a cyanopeptide-analogue with trypsin activating properties

Radau, Gregor; Rauh, Daniel

doi:10.1016/s0960-894x(00)00101-3

Cited by 12 publications

(8 citation statements)

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“…To date, limited efforts have been made to prepare analogues of the aeruginosin natural products 74. 99–104 Selected examples are depicted in Scheme . Mainly aeruginosins 298A and 98B have been explored as starting points for the synthesis of new synthetic aeruginosin‐like serine protease inhibitors 74.…”

Section: Aeruginosin Analoguesmentioning

confidence: 99%

“…Mainly aeruginosins 298A and 98B have been explored as starting points for the synthesis of new synthetic aeruginosin‐like serine protease inhibitors 74. 99–104 In one of these studies by Radau and co‐workers99 a trypsin activator rather than inhibitor was surprisingly identified. Radau and co‐workers99–101 used L ‐proline as a core structure instead of the synthetically more demanding Choi.…”

Section: Aeruginosin Analoguesmentioning

confidence: 99%

“…99–104 In one of these studies by Radau and co‐workers99 a trypsin activator rather than inhibitor was surprisingly identified. Radau and co‐workers99–101 used L ‐proline as a core structure instead of the synthetically more demanding Choi. More recently, Radau and co‐workers101b have reported analogues possessing selective, albeit weak, inhibition against thrombin versus trypsin ( 111 and 112 , Scheme ).…”

Section: Aeruginosin Analoguesmentioning

confidence: 99%

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Chemistry and Biology of the Aeruginosin Family of Serine Protease Inhibitors

2008

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The aeruginosins have been isolated from marine sponges and cyanobacterial waterblooms, sources that are phylogenetically distinct and the bodies of water are geographically well-separated. The aeruginosins comprise a central hydroxy- (or dihydroxy-) octahydroindole carboxamide core unit, onto which are appended unusual amino acids on the carboxy and amino termini as part of the linear peptide array. Potent inhibitory activity of serine proteases in vitro is exhibited by some of the aeruginosins as a result of the presence and proper deployment of three important pharmacophoric subunits: a P1 arginine mimetic, and two hydrophobic residues with interaction sites designated as P2 and P3. In this article, we provide the first comprehensive review on the chemistry and biology of the aeruginosins, with an emphasis on their sources, structural revisions, and total syntheses.

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Section: Aeruginosin Analoguesmentioning

confidence: 99%

Section: Aeruginosin Analoguesmentioning

confidence: 99%

Section: Aeruginosin Analoguesmentioning

confidence: 99%

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Chemistry and Biology of the Aeruginosin Family of Serine Protease Inhibitors

2008

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“…The first attempt to synthesize precursor 11 (Scheme 1) started with the transformation of HPA (3-[4-hydroxyphenyl]propionic acid, 7) into its succinimide ester 8, which is enabled to react with completely unprotected L-isoleucine to give the appropriate N-acylated amino acid 9 [16]. As expected, 11 was not available through the connection of 9 and 10 without any protection or blockade of the secondary amino group of piperazine in 10.…”

Section: Synthesesmentioning

confidence: 99%

New Cyanopeptide‐Derived Low MolecularWeight Thrombin Inhibitors

Radau¹,

Gebel²,

Rauh³

2003

Archiv der Pharmazie

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Thrombosis is the result of defective regulation of the hemostasis system. This cardiovascular disorder may lead to deep vein thrombosis, myocardial infarction, and stroke. The majority of current drug research is focused on finding inhibitors of thrombin - the global player in hemostasis. In our work, we emphasize investigation of the marine environment to yield new lead structures from marine organisms like blue-green algae (cyanobacteria). This article deals with the design, syntheses, and inhibition tests of new low molecular weight thrombin inhibitors utilizing cyanopeptides, the secondary metabolites of cyanobacteria with interesting biological activities, as new lead structures. Starting with aeruginosin 98-B (2) as a lead structure, we have developed and synthesized new, selective acting inhibitors of thrombin (RA-1001 and RA-1002), which are suitable targets for further structure-activity studies.

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“…In previous reports, we described the syntheses of the thrombin inhibitors RA-1001 and RA-1002 as well as their precursors (RA-1003 and RA-1004) utilizing aeruginosin 98-B -a secondary metabolite from cyanobacterium Microcystis aeruginosa -as the starting lead structure ( Figure 1) [8][9]. Compounds RA-1001, RA-1002, and RA-1003 are equipotent thrombin inhibitors (Table 1).…”

Section: Structural Considerationsmentioning

confidence: 99%

New Cyanopeptide‐Derived Low Molecular Weight Inhibitors of trypsin‐like Serine Proteases

Radau¹,

Schermuly²,

Fritsche³

2003

Archiv der Pharmazie

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This paper deals with the design, syntheses, and inhibition tests of new low molecular weight thrombin inhibitors utilizing cyanopeptides, the secondary metabolites of cyanobacteria with interesting biological activities, as new lead structures. Starting with aeruginosin 98-B (1) as a lead structure, we have developed and synthesised new, selective acting inhibitors of serine proteases (RA-1005 and RA-1009, which are suitable targets for further structure-activity studies.

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Synthesis of a cyanopeptide-analogue with trypsin activating properties

Cited by 12 publications

References 12 publications

Chemistry and Biology of the Aeruginosin Family of Serine Protease Inhibitors

Chemistry and Biology of the Aeruginosin Family of Serine Protease Inhibitors

New Cyanopeptide‐Derived Low MolecularWeight Thrombin Inhibitors

New Cyanopeptide‐Derived Low Molecular Weight Inhibitors of trypsin‐like Serine Proteases

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