Protocol Online logo
Top : Forum Archives: : Protein and Proteomics

Did my Ab provider do me wrong? - Judging the purity of my antibody (Sep/14/2007 )

I had a company make me 3 polyclonal Ab to the same protein. I had all three affinity purified.

The first Ab was made with the total protein as antigen
The second was with a 12 AA synthesized peptide from my protein
The third was a 16 AA syn. peptide from my protein.

I can detect my positive his-tagged protein control by western, but I am having trouble detecting the same protein within a plant extract (which I know is there).

A collegue suggested making sure the majority of the 3 Ab are specific for only my protein and that no other Ab populations exist within.

He suggested spiking my his-tagged control protein into E. coli total protein and running a western using the 3 Ab as my primary Ab (of course this would be 3 separate blots).

To my surprise the 3 Ab not only bound to the spiked control protein, but also heavily to 5-8 ecoli bands as well.

My question is - is this normal or should I only be seeing my 3 affinity pure Ab binding to the control protein???

Thanks - H

-holyrail-

did you blast the aa sequences to ensure specificity for your protein?

how concentrated was your probe? if it is too concentrated you may see significant non-specific binding.

did you use tween in your solutions for the blot? this also helps reduce non-specific binding.

the antibodies bound to denatured protein (western) but not to native protein. what were they prepared and/or purified against, native or denatured?

-mdfenko-

Thanks for your reply.

Blast - I am working with an arab. stress protein - so wouldn't think much non-specific binding should occur in e. coli - especially with the Ab made from short peptides specific to my protein.

My primary Ab is 1:1000 (of a 1mg/ml stock). Followed by 1:5000 secondary

Using Invitrogen Western Breeze kit which has worked well

The one Ab was made from denatured antigen - ran lots of protein on SDS gel, cut out and sent to Ab company
THe other 2 were made from synthesized peptides - I assume this would be native (?)




QUOTE (mdfenko @ Sep 14 2007, 01:34 PM)
did you blast the aa sequences to ensure specificity for your protein?

how concentrated was your probe? if it is too concentrated you may see significant non-specific binding.

did you use tween in your solutions for the blot? this also helps reduce non-specific binding.

the antibodies bound to denatured protein (western) but not to native protein. what were they prepared and/or purified against, native or denatured?

-holyrail-

QUOTE (holyrail @ Sep 14 2007, 02:16 PM)
Thanks for your reply.

Blast - I am working with an arab. stress protein - so wouldn't think much non-specific binding should occur in e. coli - especially with the Ab made from short peptides specific to my protein.

My primary Ab is 1:1000 (of a 1mg/ml stock). Followed by 1:5000 secondary

Using Invitrogen Western Breeze kit which has worked well

The one Ab was made from denatured antigen - ran lots of protein on SDS gel, cut out and sent to Ab company
THe other 2 were made from synthesized peptides - I assume this would be native (?)

blast will compare your aa sequences with known sequences and determine degree of homology. shorter sequences are more likely to be duplicated across different proteins.

you may want to try more dilute primary antibody (1:5000, 1:10000,...; you can try a range of dilutions to find one where you geat the best signal with the least background and non-specific bands).

synthesized peptides, especially short ones, do not necessarily fold properly.

-mdfenko-