77-92Carbohydrate-based therapeutics is a rapidly
developing theme, resulting directly from the recent increase in interest in the
biological roles of carbohydrates. A fundamental requirement for successful drug
design is a detailed understanding of protein-carbohydrate interactions. This article
reports a structural bioinformatics study of several carbohydrate binding
proteins to identify common minimum principles required for the recognition of mannose,
glucose and galactose, which indeed form much or the basis for recognition of higher
sugars. The study identifies all aspartic acid -04 sugar hydroxyl interaction to
be highly conserved, which appears to be crucial for recognition of all three sugars.
Other interactions are specific to particular sugars, leading to individual fingerprints.
These fingerprints have then been used in the identification of lead compounds,
using fragment-based design approaches. The results obtained by such guided design
protocols are found to be more focused than those obtained from comparable ab-initio
design protocols. These studies, apart from providing clues about the usable
pharmacophore space for these structures, also prove that the use of fingerprints
in a fragment-based ligand design, leads to the design of a sugar-like ligand, mimicking
the natural carbohydrate ligand in each of the eight examples studied
