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Chemical Structure| 29908-03-0 Chemical Structure| 29908-03-0
Chemical Structure| 29908-03-0
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Zhou, Jujun ; Deng, Youchao ; Iyamu, Iredia D. ; Horton, John R. ; Yu, Dan ; Hajian, Taraneh , et al.

Abstract: S-Adenosyl-L-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host-pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (6e and 7), we designed an adenosine analog (11a) carrying a 3-phenylpropyl moiety at the adenine N6-amino group, and a 3-(cyclohexylmethyl guanidine)-Et moiety at the sulfur atom off the ribose ring. Compound 11a (IC50 = 0.15 μM) is 10x and 5x more potent against CamA than 6e and 7, resp. The structure of the CamA-DNA-inhibitor complex revealed that 11a adopts a U-shaped conformation, with the two branches folded toward each other, and the aliphatic and aromatic rings at the two ends interacting with one another. 11a occupies the entire hydrophobic surface (apparently unique to CamA) next to the adenosine binding site. Our work presents a hybrid knowledge-based and fragment-based approach to generating CamA inhibitors that would be chem. agents to examine the mechanism(s) of action and therapeutic potentials of CamA in C. difficile infection.

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Product Details of S-Adenosyl-L-methionine

CAS No. :29908-03-0
Formula : C15H22N6O5S
M.W : 398.44
SMILES Code : O[C@@H]([C@H]([C@H](N1C=NC2=C1N=CN=C2N)O3)O)[C@H]3C[S+](CC[C@H](N)C([O-])=O)C
Synonyms :
S-Adenosyl methionine; AdoMet; Gumbaral.
MDL No. :MFCD00871208
InChI Key :MEFKEPWMEQBLKI-AIRLBKTGSA-N
Pubchem ID :34755

Safety of S-Adenosyl-L-methionine

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338
 

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