*** For details on how to be removed from this list visit the *** *** CCP4 home page http://www.ccp4.ac.uk ***
Hi, Selective disruption of complexes is pretty hard to accomplish. There is a score of papers in drug discovery journals that deal with this kind of task, but overall the success is very uncertain. If you can design a peptide that is helical in solution by itself, and also has the right amino acids exposed to form a complex with one of the proteins, the chances are pretty good that you will disrupt the complex formation at reasonable peptide concentrations. Kon/Koff are an issue here because pre-formed complexes may take non-trivial time to disrupt, even if relative affinities between complex partners and the peptide are reasonable. Whether to use a peptide or a small molecule - this strongly depends on *why* would you want to disrupt the complex. If this is for an in vitro study then most likely almost anything goes. For in vivo, peptides can have issues (such as lack of permeation, proteolysis, etc.) that may make the design of such peptide difficult. On the other hand, peptides tend to be 'easier' on the cell from the toxicity standpoint. On top of this, design of small molecules to inhibit protein complex formation is, in my opinion, considerably more difficult than doing the same thing with peptides. So it's a balance of factors that can't be addressed explicitly until more is known about the target system and application :) Hope this helps, Artem Ex-PGO -----Original Message----- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of [EMAIL PROTECTED] Sent: Monday, May 01, 2006 12:40 PM To: [email protected] Subject: [ccp4bb]: Disrupting a protein complex with a peptide *** For details on how to be removed from this list visit the *** *** CCP4 home page http://www.ccp4.ac.uk *** Dear All : Sorry for this non-CCP4 question. I am dealing with a protein binary complex, with known structure. We know that the interaction between both partners is processed via a short helix. OK, let's imagine that we would like to disrupt this interaction in vitro. I was thinking in using a peptide that will mimic the short helix of one of the partners to block the other one. Is it a crazy idea ?. Anyone has dealed with something like that with the same approach ?. Is it better to use peptides to disrupt protein complexes, or we could use small molecules as well ?. Any rational (but easy, for dummies level) approach to design the peptide that blocks the complex formation ?. I would appreciate some help and comments about that. Many, many thanks Cheers Francisco ----------------------------------------- Francisco J. Enguita, Ph.D. Host-pathogen Interactions Group Macromolecular Crystallography Laboratory ITQB EAN, Av. da República 2781-901 Oeiras Portugal Phone : +351-21-4469663 Fax : +351-21-4433644 E-mail : [EMAIL PROTECTED] -----------------------------------------
