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We demonstrate that molecular modeling and simulation represent an effective approach to gather information on key biological processes and thus guide rational molecular design strategies.Helicobacter pylori, the most common cause of chronic gastritis, peptic ulcers, and gastric cancers, infects around half of the world's population. Although the drawbacks of antibiotic-based combination therapy are emerging, no effective vaccine is available to prevent H. pylori infections. Here, we describe the total synthesis of the unique α-(1→3)-linke