The heparin and heparan sulfate class of glycosaminoglycans (mucopolysaccharides) has an extraordinary variation in the secondary features of the disaccharide repeating units. This class of complex carbohydrates has been implicated in the modulation of numerous reactions involving enzymes, proteins and cell membranes. We have continued to characterize oligosaccharides from these glycosaminoglycans and to relate their specific chemical properties to the multiple biological functions of the macromolecule(s). The molecular basis of modulating reactions between heparin and proteins (e.g., antithrombin, tyrosine hydroxylase) is investigated by uv circular dichroism (CD) spectroscopy of the protein and its complexes with oligosaccharide modulators. Heparin has two functional domains (contained within an octadecasaccharide segment) that are able to modulate differentially the reactions between the clotting inhibitor, antithrombin (AT), and the various esterases of the clotting cascade. Using our human AT and newly-derived heparin segments of 8 to 22 saccharides, we showed that the two functional domains interact with different regions of AT. The major domain interacts with at least one 'exposed' and one 'buried' tryptophane residue of AT, while the adjacent oligosaccharide modulator appears to perturb the CD of a disulfide bond. Thus, the multifunctional action of heparin is probably related to its ability to induce conformational changes in AT. The structures of heparin and heparan sulfate oligosaccharides are investigated by low uv CD spectroscopy along with model compounds. We elucidated the saccharide sequence of the second functional domain of heparin, enabling the proposal of the sequence of the highly active, 6,500 molecular weight heparin. The multifunctional modulator consists of alternating regions of higher and lower anionic density and varies in the distance between the highly sulfated segments that flank both functional domains. This important structure-function relation may have general biological significance. Conformational aspects of these domains are explored using techniques of Induced CD spectroscopy combined with computer-calculated theoretical spectra based on the geometries of the arrays of their anionic groups. Heparan sulfate oligosaccharides from Sanfilippo patients are isolated and characterized for experiments on neuronal development.