The biological activity of streptomycin and related molecules implicated in the interaction with proteins are associated with the presence of functional guanidine groups
Aly Moussa
Anses Lyon Laboratory, France
: J Diagnos Tech Biomed Anal
Abstract
The presence of 2 functional guanidine groups was suspected to be the chemical structure of streptomycin implicated in the interaction with proteins. To prove this hypothesis, several chemicals possessing guanidine groups as dihydrostreptomycin, bis-3-aminopropylamine, guanidine hydrochloride, spermine tetra-hydrochloride and triethylenetetramine were tested for evaluating their interaction with the pathogenic prion protein (PrPsc). All of these molecules at low concentration induced a gradual increase of the molecular weight of the 3 peptides isoforms and at higher concentration aggregation and flocculation of the prion protein which can be precipitation by a low centrifugation step. The interaction of streptomycin with proteins was optimum at alkaline PH and takes place through hydrogen bond transfer between the 2 guanidine groups on streptomycin and the negatively charged amino-acids of one or several prion peptides ruling the possibility of a Schiff-base reaction. Streptomycin had proved valuable for earlier and higher immunological detection of prions in clinical samples due to protein aggregation as well as to a better attachment of antibodies to their epitopes through electric charge transfer on the protein surface. These changes of the surface electrostatic charges induced by streptomycin affect also the prion stability leading to a reduced infectivity. On the other hand the resistance to proteinase K digestion of the prion protein PrPsc in presence of streptomycin was not affected proving that the structures controlling infectivity and PK resistance are different.
Biography
Aly Moussa has obtained his BVSc from Cairo University, Egypt, Dr. Vet. Med. from Justus Liebig University, Germany and PhD from Claude Bernard University, France. He worked 4 years at IFFA-Mérieux Laboratory; Lyon- France, for 20 years was the Chief of Virology Service at the French Bovine Pathology laboratory. Then for 8 years he was concerned at the national agency for sanitary security of aliments with research on the pathogenic prion proteins. He has published many papers in the fields of virology and transmissible spongiform encephalopathy’s.
