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Hi, I haven't seen it mentioned yet. Peter Kim designed a helical peptide that jammed gp41 in HIV membrane fusion: Protein Design of an HIV-1 Entry Inhibitor Michael J. Root, Michael S. Kay, Peter S. Kim Science (2001) Vol. 291. no. 5505, pp. 884 - 888 It's probably the most expensive inhibitor on the market:-) Importantly, the helical peptide inhibits, because the helical bundle still has to be formed prior to fusion and some of the helical structure only occurs on bundle formation. So a peptide may work if the helix is not stable before protein-protein interaction. cheers, Rob Meijers Synchrotron Soleil --- Artem Evdokimov <[EMAIL PROTECTED]> wrote: > *** 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] > ----------------------------------------- > > > __________________________________________________ Do You Yahoo!? Tired of spam? Yahoo! Mail has the best spam protection around http://mail.yahoo.com
