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The chemical complexity and heterogeneity of this polysaccharide can explain the fact that, despite its widespread medical use as an anticoagulant drug, the structure\u2013function relationship of defined heparin sequences is still poorly understood. Here, we present the chemical synthesis of a library containing heparin oligosaccharides ranging from di\u2010 to hexamers of different sequences and sulfation patterns. An amine\u2010terminated linker was placed at the reducing end of the synthetic structures to allow for immobilization onto <jats:italic>N<\/jats:italic>\u2010hydroxysuccinimide activated glass slides and creation of heparin microarrays. Key features of this modular synthesis, such as the influence of the amine linker on the glycosidation efficiency, the use of 2\u2010azidoglucose as glycosylating agents for oligosaccharide assembly, and the compatibility of the protecting group strategy with the sulfation\u2010deprotection steps, are discussed. Heparin microarrays containing this oligosaccharide library were constructed using a robotic printer and employed to characterize the carbohydrate binding affinities of three heparin\u2010binding growth factors. FGF\u20101, FGF\u20102 and FGF\u20104 that are implicated in angiogenesis, cell growth and differentiation were studied. These heparin chips aided in the discovery of novel, sulfated sequences that bind FGF, and in the determination of the structural requirements needed for recognition by using picomoles of protein on a single slide. The results presented here highlight the potential of combining oligosaccharide synthesis and carbohydrate microarray technology to establish a structure\u2013activity relationship in biological processes.<\/jats:p>","DOI":"10.1002\/chem.200601103","type":"journal-article","created":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T12:29:20Z","timestamp":1161779360000},"page":"8664-8686","source":"Crossref","is-referenced-by-count":194,"title":["Preparation and Use of Microarrays Containing Synthetic Heparin Oligosaccharides for the Rapid Analysis of Heparin\u2013Protein Interactions"],"prefix":"10.1002","volume":"12","author":[{"given":"Christian","family":"Noti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"de Paz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Polito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Seeberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,11,16]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3757(20020201)114:3<426::AID-ANGE426>3.0.CO;2-Q"},{"key":"e_1_2_6_1_3","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20020201)41:3<390::AID-ANIE390>3.0.CO;2-B"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2005.05.013"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2004.11.020"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2318(01)57017-1"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200300254"},{"key":"e_1_2_6_6_2","volume-title":"Heparin\u2010Binding Proteins","author":"Conrad H. 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