Different protein-binding selectivities for N-acyl heparin derivatives having N-phenylacetyl and heterocycle analogs of N-phenylacetyl substituted in place of N-sulfo groups.
Replacing N-sulfo groups in heparin with N-arylacyl moieties has been shown to afford charge-reduced heparin derivatives that maintain affinity for select heparin-binding proteins. In this study 50% and 100% N-desulfonated heparins were selectively N-acylated with phenylacetic acid and four phenylacetic acid analogs where the phenyl ring was replaced by a heterocycle. Protein-binding studies reveal that structural differences in the ring systems of the N-acyl groups appended to heparin afford significant affects on affinity and selectivity for different heparin-binding proteins.
Huang
Liusheng
L
Division of Medicinal and Natural Products Chemistry, University of Iowa, Iowa City, IA 52242, USA.
Fernández
Cristina
C
Kerns
Robert J
RJ
D000215:Acylation; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D002240:Carbohydrate Sequence; D006493:Heparin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis; D006801:Humans; D066298:In Vitro Techniques; D007781:Lactoferrin / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010314:Partial Thromboplastin Time; D010648:Phenylacetates / Q000737:chemistry; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014302:Trinitrobenzenesulfonic Acid
D006571:Heterocyclic Compounds; D010648:Phenylacetates; D014302:Trinitrobenzenesulfonic Acid; D006493:Heparin; D007781:Lactoferrin; C025136:phenylacetic acid