Preparation of spermine conjugates with acidic retinoids with potent ribonuclease P inhibitory activity

Investigation on Toxicity and Teratogenicity in Rats of a Retinoid‐Polyamine Conjugate with Potent Anti‐Inflammatory Properties

“…Although no detailed mechanistic studies have been so far carried out, it appears from many existing experimental evidence that RASP shows more potent pharmacological effect to the parent retinoid retinoic acid (atRA) with significantly lower toxic effects. Indeed, in several experiments RASP has shown notably improved activity compared to a simple mixture of free atRA and spermine (SPM) in the ratio 2:1 (Magoulas et al., ). In addition, although the currently used retinoids cause skin inflammation, this compound is expected on the contrary to show an anti‐inflammatory activity (Papaioannou et al., ; Hadjipavlou et al., ).…”

“…It should be noted that the clinical application of retinoids to the management of recalcitrant and incurable in the past neoplastic, immunological, and keratinization disorders has introduced a real revolution in dermatological and other medical fields (Stefanaki et al, 2005;Strauss et al, 2007;Carr et al, 2011;Sanz and Lo-Coco, 2011;Sbidian et al, 2011). Although no detailed mechanistic studies have been so far carried out, it appears from many existing experimental evidence that RASP shows more potent pharmacological effect to the parent retinoid retinoic acid (atRA) with significantly lower toxic effects. Indeed, in several experiments RASP has shown notably improved activity compared to a simple mixture of free atRA and spermine (SPM) in the ratio 2:1 (Magoulas et al, 2009). In addition, although the currently used retinoids cause skin inflammation, this compound is expected on the contrary to show an anti-inflammatory activity Hadjipavlou et al, 2010).…”

“…N 1 , N 12 ‐Bis( all‐trans ‐retinoyl)spermine (RASP) was synthesized and isolated in the form of its corresponding bishydroxysuccinimidate salt (MW: 997.35), as previously described (Magoulas et al., ). RASP was diluted in ddH 2 O under mild stirring by heating at 40–50°C at a final concentration of 5 mg/ml.…”

“…), namely N 1 , N 12 ‐bis( all‐trans ‐retinoyl)spermine (RASP), consisting of two molecules of atRA covalently attached at positions N 1 and N 12 of a molecule of the natural polyamine spermine (SPM) (Papaioannou et al., ). RASP exhibited a considerable improvement of biological activity compared to the parent retinoid or a combination of free SPM and atRA, when tested for its inhibitory effect on the RNase P activity isolated from D. discoideum (Magoulas et al., ).…”

Synthesis of peptide conjugates with vitamins for induction of antigen‐specific immunotolerance

“…Peptide was synthesized on NovaSyn TGA resin at a 0. vD3-succinic acid-NHS) were synthesized according to literatures. 18,19 The lysine residue-protected peptide (1 mM) and vitamin-NHS (10 mM) were dissolved in dimethylformamide (DMF). N,N-Diisopropylethylamine (10 mM) was added to the solution and reacted at room temperature overnight under nitrogen.…”