Chapter 11. Antithrombotic Agents

Fleming, John; MacNintch, John E.

doi:10.1016/s0065-7743(08)60999-9

Cited by 1 publication

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“…Adenylosuccinic acid (6-aspartopurine-9-ribosyl-5'-monophosphate) is an intermediate product in the amination of inosinic acid (IMP) to adenylic acid (AMP)' 2 '. Synthetic W-(6-purinyl)amino acids, available by aminolysis of 6-chloropurine with amino acids' 2 " 5 ', show a wide range of biological activities: some of them are antimetabolites in cancer chemotherapy' 3 ' 5 ', others are antithrombotic agents' 6 ' or have cytokinin-like activities' 7 '. Purines, especially those containing an hydrophobic substituent in the N-9-position, show immunomodulator activities as well as antiviral and antitumour activities.…”

Section: Synthese Und Einige Biologische Eigenschaften Von N-/6-purinmentioning

confidence: 99%

The Synthesis and Some Biological Properties of N-(6-Purinyl)peptides

Schäfer¹,

Büllesbach²,

Jollès³

et al. 1986

Biological Chemistry Hoppe-Seyler

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The chemical synthesis and biological properties of N-(6-purinyl)peptides are described. W-(6-Purinyl)amino-acid derivatives were synthesized and condensed with amino acid esters and peptide esters using the dicyclohexylcarbodiimide/AMiydroxysuccinimide method. The products were isolated via gel filtration on Sephadex G-10 in 0.05M NH 4 HCO 3 followed by either ion exchange chromatography on SP-Sephadex or by preparative HPLC. The methyl esters were saponified and the tertbutyl ester group was removed by treatment with trifluoroacetic acid without damaging the purinyl residue. AK6-Purinyl)peptides were characterised by Chromatographie and spectroscopic methods.Acid hydrolysis of AK6-purinyl)-L-amino acids caused the racemization of the neighbouring L-amino acid. Model studies were performed with AH6-purinyl)-L-alanine, AH6-purinyl)-Dalanine, AH6-purinyl)-L-alanyl-L-leucine and Af-(6-purinyl)-D-alanyl-L-leucine. After acid hydrolysis the AK6-purinyl)amino acids were totally racemized and the 7V-(6-purinyl)dipeptides formed 14% of the enantiomer of alanine.The 7V-(6-purinyl)-co-amino acids and the 7V-(6-purinyl)peptides were screened in a limited number of tests as immunomodulators (antibody-secretion, phagocytosis, cytostatic activity of macrophages) and as cytotoxic agents. Synthese und einige biologische Eigenschaften von N-/6-PurinyDpeptidenZusammenfassung: Die Darstellung und biologische Eigenschaften einiger 7V-(6-Purinyl)peptide werden beschrieben. AM6-Purinyl)aminosäuren wurden synthetisiert und mit Aminosäure-und Peptidestern nach der Dicyclohexylcarbodiimid/A^Hydroxysuccinimid-Methode kondensiert. Mittels Gelchromatographie an Sephadex G-10 in 0.05M NH 4 HCO 3 und lonenaustauschchromatographie an SPSephadex oder präparativer HPLC konnten die Produkte rein erhalten werden. Methylester wurden verseift; te/t-Butylester ließen sich mittels Trifluoressigsäure abspalten, ohne daß eine Schädigung des Purinringes beobachtet wurde. Die AH6-Purinyl)peptide wurden mittels chromatographischer und spektroskopischer Methoden charakterisiert. Die saure Hydrolyse von 7V-(6-Purinyl)-L-aminosäuren führte zu einer Razemisierung der ankondensierten Aminosäure, die möglicherweise durch den Purinring kataly-

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Section: Synthese Und Einige Biologische Eigenschaften Von N-/6-purinmentioning

confidence: 99%