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Titolo:
The activation of fibroblast growth factors by heparin: Synthesis, structure, and biological activity of heparin-like oligosaccharides
Autore:
de Paz, JL; Angulo, J; Lassaletta, JM; Nieto, PM; Redondo-Horcajo, M; Lozano, RM; Gimenez-Gallego, G; Martin-Lomas, M;
Indirizzi:
CSIC, Inst Invest Quim, Grp Carbohidratos, Seville 41092, Spain CSIC Seville Spain 41092 t Quim, Grp Carbohidratos, Seville 41092, Spain CSIC, Ctr Invest Biol, E-28006 Madrid, Spain CSIC Madrid Spain E-28006CSIC, Ctr Invest Biol, E-28006 Madrid, Spain
Titolo Testata:
CHEMBIOCHEM
fascicolo: 9, volume: 2, anno: 2001,
pagine: 673 - 685
SICI:
1439-4227(20010903)2:9<673:TAOFGF>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
FGF RECEPTOR DIMERIZATION; NMR SOLUTION CONFORMATION; L-IDURONIC ACID; ANTITHROMBIN-III; PENTASACCHARIDE FRAGMENT; CHEMICAL SYNTHESIS; HIGH-AFFINITY; SIGNAL-TRANSDUCTION; MITOGENIC ACTIVITY; CRYSTAL-STRUCTURE;
Keywords:
conformation analysis; growth factor activation; heparin; oligosaccharides; synthesis design;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
77
Recensione:
Indirizzi per estratti:
Indirizzo: Martin-Lomas, M CSIC, Inst Invest Quim, Grp Carbohidratos, Isla Cartuja,Americo Vespucio S-N, Seville 41092, Spain CSIC Isla Cartuja,Americo VespucioS-N Seville Spain 41092
Citazione:
J.L. de Paz et al., "The activation of fibroblast growth factors by heparin: Synthesis, structure, and biological activity of heparin-like oligosaccharides", CHEMBIOCHEM, 2(9), 2001, pp. 673-685

Abstract

An effective strategy has been designed for the synthesis of oligosaccharides of different sizes structurally related to the regular, region of heparin; this is illustrated by the preparation of "hexasaccharide 1 and octasaccharide 2. This synthetic strategy provides the oligosaccharide sequence containing a D-glucosamine unit at the nonreducing end that is not available either by enzymatic or chemical degradation of heparin. It may permit, after slight modifications, the preparation of oligosaccharide fragments with different charge distribution as well. NMR spectroscopy and molecular dynamics simulations have shown that the overall structure of 1 in solution is a stable right-hand helix with four residues per turn. Hexasaccharide 1 and, most likely, octasaccharide 2 are, therefore, chemically well-defined structural models of naturally, occurring heparin-like oligosaccharides for Use in binding and biological activity studies. Both compounds 1 and 2 induce the mitogenic activity of acid fibroblast growth factor (FGF1), with the half-maximum activating concentration of 2 being equivalent to that of heparin. Sedimentation equilibrium analysis with compound 2 suggests that heparin-induced FGF1 dimerization is not an absolute requirement for biological activity.

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Documento generato il 26/01/20 alle ore 16:07:20