Pentacovalent phosphorus-containing model of a P(V) cyclic nucleotide intermediate. Non-chair conformation of the phosphorus-containing ring

✍ Scribed by Jaehoon H. Yu; Wesley G. Bentrude

• Publisher: Elsevier Science
• Year: 1989
• Tongue: French
• Weight: 298 KB
• Volume: 30
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)99646-1

✦ Synopsis

Suaraary: A cyclic nucleotide model system (3) for P(V) CAMP-substrate or CAMP-enzyme adducts is shown by 'H NMR analysis to be totally in a twist conformation (3b). The stereochemistry of hydrolysis of CAMP by phosphodiesterases (PDE) has been wellstudied,' as have the structural requirements for the binding of CAMP to the active sftes of both protein kinases and PDE's.* However, little if any attention has been given to possible changes in the conformation of the phosphate ring on binding or the potential conformations of the pentacovalent phosphorus P(V) enzyme-CAMP or Substrate-CAMP adducts proposed as intermediates in the interactions of CAMP with both of these enzyme systems. 293 Recently we showed that Karplus-like 3JHP coupling relationships are operative for P(V) coordination and that in solution the 1,3,2-oxazaphosphorinane ring of 1 populates a i T ,OCH(CFS)* M-%(-j n'e b + CF, CF, 0 9 CH,O--'P-O CH,O"OCH, 3 4 non-chair conformation approximated by structure 2.4 However, up to now assignments of conformation to P(V) 1,3,2-dioxaphosphorinane rings have not been made in solution. We report here that indeed the equilibrium for the system 3a = 3b, within experimental error, completely favors 3b. This is of particular importance, because 3 serves as a model for CAMP itself. Thus the cyclic 3',5'-monophosphate diester corresponding to 3 has been shown5 to possess the same 5 kcal/mole of ring strain , engendered by the trans ring fusion, attributed to CAMP which could strongly influence the conformational equilibrium. CH(CF,), CF, CF 3 CF, 3a