Erfolge mit Einem Neuartigen Depotinsulin Ohne Protaminzusatz (Surfen-Insulin)

Umber, F.; Störring, F. K.; Follmer, W

doi:10.1007/bf01775866

Cited by 26 publications

(10 citation statements)

References 3 publications

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“…Surfen was also used as an excipient added to an acidic solution of insulin to prepare soluble complexes for therapeutic purposes. Surfen insulins of intermediate and long duration of action had been widely administered in Europe for diabetic patients . Apart from a single study on the development of lymphoma in mice fed with high doses of surfen over a prolonged period, only sporadic cutaneous allergic reactions to surfen‐containing depot‐insulins have been reported in humans .…”

Section: Methodsmentioning

confidence: 99%

“…Surfen insulins of intermediate and long duration of action had been widely administered in Europe for diabetic patients. 2 Apart from a single study on the development of lymphoma in mice fed with high doses of surfen over a prolonged period, 3 only sporadic cutaneous allergic reactions to surfen-containing depot-insulins have been reported in humans. 4 After many decades, the discovery of the C5a anaphylatoxin inhibitory potential of surfen led to the renaissance of its research.…”

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confidence: 99%

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Glycosaminoglycan and DNA Binding Induced Intra‐ and Intermolecular Exciton Coupling of the bis‐4‐Aminoquinoline Surfen

Zsila

2015

Chirality

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Despite the diverse biological activities of the glycosaminoglycan (GAG) antagonist surfen, the molecular details of its interaction with biomacromolecules remain poorly understood. Therefore, heparin and DNA binding properties of surfen were studied by circular dichroism (CD) and UV absorption spectroscopy methods. High-affinity (Ka ~ 10(7) M(-1)) association of surfen to the chiral heparin chain gives rise to a characteristic biphasic CD pattern due to the conformational twist of the aminoquinoline moieties around the central urea bridge. At higher drug loading, intermolecular stacking of surfen molecules alters the induced CD profile and also provokes strong UV hypochromism. In contrast to the right-handed heparin template, binding of surfen to the left-helicity chondroitin sulfate chains produces inverted CD pattern. Large UV hypochromism as well as polyphasic induced ellipticity bands indicate that surfen intercalates between the base pairs of calf-thymus DNA. Extensive CD spectroscopic changes observed at higher drug binding ratios refer to cooperative binding interactions between the intercalated drug molecules. The inherent conformational flexibility of surfen demonstrated here for the first time is important in its binding to distinct macromolecular targets and should be considered for rational drug design of novel GAG antagonists.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Glycosaminoglycan and DNA Binding Induced Intra‐ and Intermolecular Exciton Coupling of the bis‐4‐Aminoquinoline Surfen

Zsila

2015

Chirality

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“…Surfen (bis-2-methyl-4-amino-quinolyl-6-carbamide) was first described in 1938 as an excipient for the production of depot insulin (16). Subsequent studies have shown that surfen can block C5a receptor binding (17) and lethal factor (LF) produced by anthrax (18).…”

mentioning

confidence: 99%

Surfen, a small molecule antagonist of heparan sulfate

Schuksz

Fuster²,

Brown³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

155

152

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In a search for small molecule antagonists of heparan sulfate, we examined the activity of bis-2-methyl-4-amino-quinolyl-6-carbamide, also known as surfen. Fluorescence-based titrations indicated that surfen bound to glycosaminoglycans, and the extent of binding increased according to charge density in the order heparin > dermatan sulfate > heparan sulfate > chondroitin sulfate. All charged groups in heparin (N-sulfates, O-sulfates, and carboxyl groups) contributed to binding, consistent with the idea that surfen interacted electrostatically. Surfen neutralized the anticoagulant activity of both unfractionated and low molecular weight heparins and inhibited enzymatic sulfation and degradation reactions in vitro. Addition of surfen to cultured cells blocked FGF2-binding and signaling that depended on cell surface heparan sulfate and prevented both FGF2-and VEGF 165-mediated sprouting of endothelial cells in Matrigel. Surfen also blocked heparan sulfate-mediated cell adhesion to the Hep-II domain of fibronectin and prevented infection by HSV-1 that depended on glycoprotein D interaction with heparan sulfate. These findings demonstrate the feasibility of identifying small molecule antagonists of heparan sulfate and raise the possibility of developing pharmacological agents to treat disorders that involve glycosaminoglycan-protein interactions.antithrombin ͉ glycosaminoglycans ͉ growth factors ͉ viral infection ͉ angiogenesis

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“…The biocompatibility of surfen, based on early studies of surfen as an excipient for depot insulin, 117 encourages further research of its neutralizing activity. However, due to this compound’s relatively low efficacy (micromolar range), the design and synthesis of more selective and potent analogs was undertaken (Figure 9).…”

Section: Targeting Heparan Sulfate-protein Interactionsmentioning

confidence: 99%

Targeting heparin and heparan sulfate protein interactions

2017

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Heparin and heparan sulfate glycosaminoglycans are long, linear polysaccharides that are made up of alternating dissacharide sequences of highly sulfated uronic acid and amino sugars. Unlike heparin, which is only found in mast cells, heparan sulfate is ubiquitously expressed on the cell surface and in the extracellular matrix of all animal cells. These negatively-charged carbohydrate chains play essential roles in important cellular functions such as cell growth, adhesion, angiogenesis, and blood coagulation. However, these biomolecules are also involved in pathophysiological conditions such as pathogen infection and human disease. This review discusses past and current methods for targeting these complex biomolecules as a novel therapeutic strategy to treating disorders such as cancer, neurodegenerative diseases, and infection.

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Erfolge mit Einem Neuartigen Depotinsulin Ohne Protaminzusatz (Surfen-Insulin)

Cited by 26 publications

References 3 publications

Glycosaminoglycan and DNA Binding Induced Intra‐ and Intermolecular Exciton Coupling of the bis‐4‐Aminoquinoline Surfen

Glycosaminoglycan and DNA Binding Induced Intra‐ and Intermolecular Exciton Coupling of the bis‐4‐Aminoquinoline Surfen

Surfen, a small molecule antagonist of heparan sulfate

Targeting heparin and heparan sulfate protein interactions

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