ª 2008 The Authors Journal compilation ª 2008 Blackwell Munksgaard doi: 10.1111/j.1747-0285.2008.00741.x
The Structure of Glycosaminoglycansand their Interactions with Proteins
Neha S. Gandhi1,2 and Ricardo L. Mancera1,2,3,*
Western Australian Biomedical Research Institute, Curtin University of Technology, GPO Box U1987, Perth, WA6845, Australia 2 School of Biomedical Sciences, Curtin University of Technology, GPO Box U1987, Perth, WA 6845, Australia 3 School of Pharmacy, Curtin University of Technology, GPO Box U1987, Perth,WA 6845, Australia *Corresponding author: Ricardo L. Mancera firstname.lastname@example.org
Glycosaminoglycans (GAGs) are important complex carbohydrates that participate in many biological processesthrough the regulation of their various protein partners. Biochemical, structural biology and molecular modelling approaches have assisted in understanding the molecular basis of such interactions,creating an opportunity to capitalize on the large structural diversity of GAGs in the discovery of new drugs. The complexity of GAG–protein interactions is in part due to the conformational ﬂexibility andunderlying sulphation patterns of GAGs, the role of metal ions and the effect of pH on the afﬁnity of binding. Current understanding of the structure of GAGs and their interactions with proteins ishere reviewed: the basic structures and functions of GAGs and their proteoglycans, their clinical signiﬁcance, the three-dimensional features of GAGs, their interactions with proteins and the molecularmodelling of heparin binding sites and GAG–protein interactions. This review focuses on some key aspects of GAG structure–function relationships using classical examples that illustrate the speciﬁcityof GAG–protein interactions, such as growth factors, anti-thrombin, cytokines and cell adhesion molecules. New approaches to the development of GAG mimetics as possible new glycotherapeutics are...