Is the introduction of labeling bad while detecting small molecules? If yes, what are the major disadvantages of using labels for signal amplification in the detection of small molecular weight (
The problem of adding a tag to a small molecule is that it can interfere with its function, location, interactions, with other molecules. But all those things are going to depend of where are you attaching the tag and were is the functional region of your molecule, and how your tag alter its structure. So the effect of the tag is hardly predictable.
If you have a concern on that and you are only interested in knowing if your molecule is getting expressed you can add the tag separated of your molecule as a bicistronic plasmid, or with a P2A sequence. That way you can check which cells are expressing your plasmid and therefore your protein. However, if you want to localize your protein inside of the cell that approach is not going to be useful.
For a given size label, the effect on molecular properties will depend on the size of the molecule you want to label. This is even true for isotope effects, they are much stronger for 2H/1H than for 13C/12C. In addition, for a small molecule the chances that the label sterically interferes with binding of the molecule into the pocket of its receptor are much larger than for, say, a big protein.