Drug design pharmacophore model

Li H, Sutter J, Hoffmann R. HypoGen an automated system for generating 3D predictive pharmacophore models. In Gtiner OF, editor. Pharmacophore perception, development and use in drug design., La Jolla International University Line, 2000. p. 173-89. 

Robust peptide-derived approaches aim to identify a small drug-like molecule to mimic the peptide interactions. The primary peptide molecule is considered in these approaches as a tool compound to demonstrate that small molecules can compete with a given interaction. A variety of chemical, 3D structural and molecular modeling approaches are used to validate the essential 3D pharmacophore model which in turn is the basis for the design of the mimics. The chemical approaches include in addition to N- and C-terminal truncations a variety of positional scanning methods. Using alanine scans one can identify the key pharmacophore points D-amino-acid or proline scans allow stabilization of (i-turn structures cyclic scans bias the peptide or portions of the peptide in a particular conformation (a-helix, (i-turn and so on) other scans, like N-methyl-amino-acid scans and amide-bond-replacement (depsi-peptides) scans aim to improve the ADME properties." ... 

Li, H., Sutter, J., Hoffinann, R. (2000) HypoGen an automated system for generating predictive 3D Pharmacophore Models. Pharmacophore Perception, Development, and use in Drug Designers (Giiner, . F., ed.), International University Line, La Jolla, CA. 

It is possible that QSAR, an empirical correlation of the data, may provide a pharmacophoric model that will be useful in next-generation drug design within this class. In such an approach, it is hoped that many of the factors which define antimalarial potency can be correlated with the structures of the analogues, and the resulting model, if valid, could be used as a predictive tool. 

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