Mapping of the epitope/paratope interactions of a monoclonal antibody directed against adenosine 3',5'-monophosphate.
A series of systematically modified cyclic AMP (cAMP) analogues, including newly synthesized benzimidazole ribofuranosyl 3',5'-monophosphates was used to map the essential molecular interactions between cAMP and the monoclonal antibody 4/2C2 (mab 4/2C2) directed against 2'-O-succinoyl cAMP [Colling, Gilles, Nass, Moka & Jaenicke (1988) Second Messengers Phosphoproteins 12, 123-133]. Its paratope binds the purine base in syn conformation by dipole-dipole interactions and hydrophobic forces and/or stacking interactions. The ribose phosphate moiety is recognized by a combination of charge interactions and H-bonds to the exocyclic and the 5'-oxygen atoms and a hydrophobic interaction at the 2'-position. There is no regioselectivity for the exocyclic oxygen atoms. Compared with the known types of binding, mab 4/2C2 thus shows a new combination of molecular interactions which may be the basis of its strikingly specific recognition and binding of the cyclic adenylates. On this account mab 4/2C2 may become an important tool in studies on cAMP metabolism.
Nass
N
N
Institute of Biochemistry, University of Cologne, Köln, Federal Republic of Germany.
Colling
C
C
Cramer
M
M
Genieser
H G
HG
Butt
E
E
Winkler
E
E
Jaenicke
L
L
Jastorff
B
B
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001666:Binding Sites, Antibody / Q000737:chemistry; D002846:Chromatography, Affinity; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D008968:Molecular Conformation; D011953:Receptors, Cyclic AMP / Q000737:chemistry
D000911:Antibodies, Monoclonal; D000939:Epitopes; D011953:Receptors, Cyclic AMP; D000242:Cyclic AMP