Structure-based design of six novel classes of nonpeptide antagonists of the bradykinin B2 receptor

Requirement for Core 2 O-Glycans for Optimal Resistance to Helminth Infection

“…Svensson et al further demonstrated that T H cell migration to the large intestine was dependent upon Gαi-coupled receptors, as treatment with pertussis toxin abrogated the accumulation of T H cells in the large intestine [9]. However, since CCL2 has also been shown to directly promote T H 2 cell responses [10], [11] and since pertussis toxin can induce IL-12 and T H 1 differentiation [12], it has remained unclear whether defective T H cell migration to the large intestine was directly affected by these treatments. In aggregate, the examples cited here highlight the fact that specific receptors and molecules involved in T H migration to the large intestine have not been identified.…”

Scaffold Design Using Computational Chemistry

“…CAVEAT was initially developed for the design of conformationally constrained peptides and peptidomimetics [19,[21][22][23] but has found more recent application in drug design [24,25], the design of chiral ligands for asymmetric catalysis [26,27], and a simple bifunctional catalyst [28]. The first example of the application of CAVEAT to small-molecule receptor design is illustrated in Fig.…”

Translating peptides into small molecules

“…20 This approach has been used in devising inhibitors of Factor Xa 21 and antagonists of the bradykinin B2 receptor. 22 A pharmacophore model can be constructed directly from the information available from the structure of a complex between a peptidic ligand and its target protein, which can reveal which interactions are productive and necessary for binding the ligand. Functionalities involved in the interaction pattern between the target and the ligand are called features.…”