Receptor site points

The hypothetical enantiophore queries are constructed from the CSP receptor interaction sites as listed above. They are defined in terms of geometric objects (points, lines, planes, centroids, normal vectors) and constraints (distances, angles, dihedral angles, exclusion sphere) which are directly inferred from projected CSP receptor-site points. For instance, the enantiophore in Fig. 4-7 contains three point attachments obtained by ... 

Fig. 4.2 Catalyst feature definition applied to a simple molecule, illustrating the inclusion of receptor site-points in the pharmacophore definition.

Fig. 7. DOCK site point breakdown for the kinase receptor study. Three primary critical regions were defined (1) adenine acceptor zone, (2) adenine donor zone, (3) kinase ATP inhibitor rear hydrophobic pocket binding region. Adapted from ref. 70.

The influence of chain length and side-chain modifications of ACTH-derived peptides on active avoidance behaviour in rats will be discussed. H-Met(02)-Glu-His--Phe-D-Lys-Phe-OH (Org 2766) emerged from these studies as an orally active peptide with an increased potency and selectivity of action. Physico-chemical data (from the literature) on the reference peptide ACTH--(4-10) did not point to a preferred conformation in solution, whereas in the crystalline state an antiparallel 3-pleated sheet structure was found. At the receptor site we suggested an a-helical conformation in which the Phe and Met residues are close together. Additional support for this suggestion came from the behavioural activity of [des-Tyr", Met ]enkephalin and of cyclo--(-Phe-Met-cAhx-), eAhx merely serving as a spacer. 

All the mechanisms we have encountered, which affect the way in which a drug is handled by the body, are important for one major reason - they all work together to determine how much drug is present at any given time at the point in the body where the drug acts - its effector site. Commonly this is at a receptor site in particular cells and organs, and the... 

These properties dictate the therapeutic, toxic, and metabolic characteristics of the overall drug molecule. These properties also completely control the ability of the drug to withstand the arduous journey from the point of administration to the receptor site buried deep within the body. These physical properties of drug molecules may be categorized into the following major groupings ... 

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