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  • Info Mapping of cAMP Receptors

Analogues for Characterization of cyclic AMP Binding Proteins

Fig. 1: Positions for the chemical modification of cyclic AMP

Meaningful selected analogues of cyclic AMP are extremely useful for mapping studies of different cAMP receptor proteins in order to get information about the essential corresponding molecular forces and their positions in the cyclic AMP moiety:

Besides important insights in the binding principles of the receptor, the practical results of successful mapping studies include the determination of positions where a spacer for affinity chromatography is tolerated, where fluorescent markers can be attached and which chemical modifications are allowed for potential analogues.

BIOLOG offers so many different analogues of cyclic AMP, that modifications for nearly each position of the second messenger are available.

The following table gives examples for cyclic AMP analogues suitable for mapping studies (Link to corresponding cyclic GMP anlogues).

 

Position Suitable Analog Effects

Adenine N1

NO-cAMP

N1 electron pair lacking

Adenine C2

2-Cl-cAMP

Steric effects, dipole

Adenine N3

3-deaza cAMP (inquire)

N3 electron pair lacking

Adenine N6

cPuMP
cIMP
6-Phe-cAMP

No hydrogen bonding via amino group
hydrogen bond donor/acceptor potential changed
Steric/dipole effects

Adenine N7

7-deaza-cAMP

N7 electron pair lacking

Adenine C8

8-Br-cAMP
8-CPT-cAMP

Syn/anti equilibrium
Steric effects

Ribose 2'- O

2'-dcAMP
MANT-cAMP
2'-O-Me-cAMP

No hydrogen bonding at 2'-OH
Steric effects

Ribose 3'- O

3'-NH-cAMP (inquire)

H-bridge donor/acceptor potential changed

Ribose 5'- O

5'-NH-cAMP (inquire)

H-bridge donor/acceptor potential changed

Phosphate ORp

Rp-cAMPS

Sulfur/oxygen exchange (exocyclic equatorial position at phosphorus)

Phosphate OSp

Sp-cAMPS

Sulfur/oxygen exchange (exocyclic axial position at phosphorus)

Phosphate O -

cAMP-AM, cAMP-Bn

No negative charge at phosphorus

Selected References:
For an extended list of articles on mapping of cyclic nucleotide-responsive receptors, please refer to B. Jastorff, University of Bremen, publication list.

 

Mapping of Protein Kinase A:

1

Jastorff, B. in Cyclic Nucleotides and Therapeutic Perspect., (G. Cehovic and G.A. Robinson Ed.), 85 - 95, Pergamon Press, Oxford, 1979 : "Systematic Variations on the Structure of Adenosine- 3', 5'- cyclic phosphate. A Rational Approach to Protein Ligand Interactions"

2

Døskeland, S.O.; Øgreid, D.; Ekanger, R.; Sturm, P.A.; Miller, J.P.; Suva, R.H., Biochemistry 22, 1094 - 1101 (1983): "Mapping of the Two Intrachain Cyclic Nucleotide Binding Sites of Adenosine Cyclic 3', 5'- Phosphate Dependent Protein Kinase I"

3

Dostmann, W.R.G.; Taylor, Susan S.; Genieser, H.-G.; Jastorff, B.; Døskeland, S.O.; Øgreid, D., J. Biol. Chem., 265, 10484 - 10491 (1990): "Probing the Cyclic Nucleotide Binding Sites of cAMP-Dependent Protein Kinase I and II with Analogs of Adenosine 3', 5' -Cyclic Phosphorothioates"

 

Mapping of Cyclic Nucleotide Phosphodiesterases:

1

Erneux, C.; Miot, F.; Van Haastert, P.J.M.; Jastorff, B., J. Cyclic Nucleotide Protein Phosphorylation Res., 10, 463 - 472 (1985) : "The Binding of Cyclic Nucleotide Analogs to a Purified Cyclic GMP- Stimulated Phosphodiesterase from Bovine Adrenal Tissue"

2

Braumann, T.; Erneux, C.; Petridis, G.; Stohrer, W.D.; Jastorff, B., Biochim. Biophys. Acta, 871, 199 - 206 (1986) : "Hydrolysis of Cyclic Nucleotides by a Purified cGMP- stimulated Phosphodiesterase: Structural Requirements for Hydrolysis"

3

Van Lookeren Campagne, M.M.; Villalba Diaz, F:; Jastorff, B.; Winkler, E.; Genieser, H.-G.; Kessin, R.W., J. Biol. Chem., 265, 5847 - 5854 (1990): "Characterization of the Yeast Low Km cAMP- Phosphodiesterase With cAMP Analogues"

4

Butt, E., Beltman, J., Becker, D.E., Jensen, G.S., Jastorff, B., and Beavo, J.A., Mol. Pharmacol., 47, 340 - 347 (1995) : "Characterization of Cyclic Nucleotide Phosphodiesterases Using cAMP Analogs: The Topology of the Catalytic Site and Comparison to other cAMP-binding Proteins"

 

Mapping of Catabolite Repression Protein (CRP/CAP):

1

Scholübbers, H.G.; Van Knippenberg, P.H.; Baraniak,J.; Stec, W.J.; Morr, M.; Jastorff, B., Eur. J. Biochem., 138, 101 - 109 (1984) : "Investigations on Stimulation of Lac Transciption in Vivo in Escherichia Coli by cAMP Analogs"

2

Scholübbers, J.G., Ph.D. Thesis, 103 pp, University of Bremen (1985): "Untersuchungen der biologischen Eigenschaften von Cyclonukleotid-Analogen in Escherichia coli"

 

Mapping of Other cAMP-binding Proteins :

1

Naß, N.; Colling, C.; Cramer, M.; Genieser, H.- G.; Butt, E.; Winkler, E.; Jaenicke, L.; Jastorff, B., Biochem. J., 285, 129 - 136 (1992): "Mapping of the Epitope/Paratope Interactions of a Monoclonal Antibody Directed Against Adenosine- 3', 5'- monophosphate"

2

Feldwisch, O.; Lammertz, M.; Hartmann, E.; Feldwisch, J.; Palme, K.; Jastorff, B.; Jaenicke, L.:, Eur. J. Biochem., 228, 480 - 489 (1995): "Purification and Characterization of a cAMP-binding Protein of Volvox carteri f. nagariensis Iyengar"