Conformational transmission in pentacoordinated phosphorus systems, modelling the activated state of cyclic AMP

✍ Scribed by Niek L. H. L. Broeders; Leo H. Koole; Henk M. Buck

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 545 KB
• Volume: 2
• Category: Article
• ISSN: 1042-7163
• DOI: 10.1002/hc.520020123

✦ Synopsis

The proposed activated state of cyclic adenosine 3',5 'monophosphate (CAMP) is modelled by two nucleoside cyclic 3'5' Pv-TBP compounds 3 and 4. The reason for the design of compound 3, in which a probe fragment (O--CH2-CH2-OCH3 group) is linked to phosphorus, was reflected in a con formational transmission effect, which occurs when the probe is located in the axis of a P'/-TBP. This means that the sixmembered 3',5'-dioxaphosphorinane ring predominantly remains in a diequatorial (e,e) orientation. In the absence of con formational transmission, as in compound 4, the 3',5'-dioxaphosphorinane ring favors an equatorial-axial (e,a) orientation. From this we conclude that the occurrence of conformational transmission can stabilize the (e,e) orientation of the 3',5'-ring. This can be o f relevance to the activation of protein kinase bv CAMP. In order to obtain more structural information from 3 and 4, we performed MNDO calculations on the models 8-10. These calculations revealed that the (e,e) orientation of the 3'3'ring is destabilized by 3-4 kcallmol compared to the (e,a) orientation. For the (e,a) geometry, the 3',5'-ring adopts a twist conformation, whereas the (e,e) orientated 3',5'-ring shows a halfkhair geometry.